- Understand the basic steps in the transcription of DNA into RNA
Transcription takes place in the nucleus. It uses DNA as a template to make an RNA (mRNA) molecule. During transcription, a strand of mRNA is made that is complementary to a strand of DNA. Figure 1 shows how this occurs.
Figure 1. Overview of Transcription. Transcription uses the sequence of bases in a strand of DNA to make a complementary strand of mRNA. Triplets are groups of three successive nucleotide bases in DNA. Codons are complementary groups of bases in mRNA.
You can also walk through the steps of transcription in this link.
Transcription takes place in three steps: initiation, elongation, and termination. The steps are illustrated in Figure 2.
Figure 2. Transcription occurs in the three steps—initiation, elongation, and termination—all shown here.
Step 1: Initiation
Initiation is the beginning of transcription. It occurs when the enzyme RNA polymerase binds to a region of a gene called the promoter. This signals the DNA to unwind so the enzyme can ‘‘read’’ the bases in one of the DNA strands. The enzyme is now ready to make a strand of mRNA with a complementary sequence of bases.
Step 2: Elongation
Elongation is the addition of nucleotides to the mRNA strand. RNA polymerase reads the unwound DNA strand and builds the mRNA molecule, using complementary base pairs. There is a brief time during this process when the newly formed RNA is bound to the unwound DNA. During this process, an adenine (A) in the DNA binds to an uracil (U) in the RNA.
Step 3: Termination
Termination is the ending of transcription, and occurs when RNA polymerase crosses a stop (termination) sequence in the gene. The mRNA strand is complete, and it detaches from DNA.
This video provides a review of these steps. You can stop watching the video at 5:35. (After this point, it discusses translation, which we’ll discuss in the next outcome.)
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Transcription and Translation Lesson Plan
Teachers' Domain: Cell Transcription and Translation
Teachers' Domain is a free educational resource produced by WGBH with funding from the NSF, which houses thousands of media resources, support materials, and tools for classroom lessons.One of these resources focuses on the topics of transcription and translation.This resource is an interactive activity that starts with a general overview of the central dogma of molecular biology, and then goes into more specific details about the processes of transcription and translation.In addition to the interactive activity, the resource also includes a background narrative and discussion questions that could be used for assessment.Although the material is designated as appropriate content for grades, 9-12, it would serve as an excellent introduction to the topic for biology majors, or would be well suited for non-biology majors at the post-secondary level. See: Teachers' Domain: Cell Transcription and Translation
The DNA Learning Center's (DNALC)
The Howard Hughes Medical Institute's DNA interactive (DNAi)
The University of Utah's Genetic Science Learning Center
The DNA Learning Center's (DNALC) website, the Howard Hughes Medical Institute's DNA interactive (DNAi) website, and the University of Utah's Genetic Science Learning Center website listed below contain excellent narrated animations describing transcription and translation. These animations are useful as a lecture supplement or for students to review on their own. The DNALC animations cover central dogma, transcription (basic and advanced), mRNA splicing, RNA splicing, triplet code and translation (basic and advanced). The DNAi modules," Reading the Code" and "Copying the Code," describe the history of the process, the scientists involved in the discovery, and the basics of the process, and also include an animation and interactive game. Particularly useful to students are the interactive animations from the University of Utah that allow one to, for example,"Transcribe/Translate a Gene"or examine the effects of gene mutation as they "Test Neurofibromin Activity in a Cell."
The DNA Learning Center's (DNALC): 3-D Animation Library
The Howard Hughes Medical Institute's DNA interactive: (DNAi): Code
The University of Utah's Genetic Science Learning Center: Transcribe and Translate a Gene
The Nature Education website, Scitable, is a great study resource for students who want to learn more about, or are having difficulty understanding, transcription and translation. The site contains a searchable library, including many "overviews" of transcription, translation, and related topics. Students have access to a Genetics "Study Pack", which provides explanations, animations, and links to other resources.In addition, Scitable has an "Ask An Expert" feature that allows students to submit specific genetics-related questions. See: Scitable
NHGRI Talking Glossary of Genetics Terms iPhone App and Website
The Talking Glossary of Genetics Terms website and iPhone app provide an easily transportable and accessible reference for your students. Many times the unfamiliar vocabulary is the major stumbling block to student comprehension. This app/site gives them a handy reference to common terms used in describing the components involved on transcription and translation.
Talking Glossary of Genetics Terms
Talking Glossary of Genetics Terms iPhone App
University of Buffalo Case Study Collection: Decoding the Flu
This "clicker case" was designed to develop students' ability to read and interpret information stored in DNA. Making use of personal response systems ("clickers") along with a PowerPoint presentation, students follow the story of "Jason," a student intern at the Centers for Disease Control & Prevention (CDC). While working with a CDC team in Mexico, Jason is the only person who does not get sick from a new strain of flu. It is up to Jason to use molecular data collected from different local strains of flu to identify which one may be causing the illness. Although designed for an introductory biology course for science or non-science majors, the case could be adapted for upper-level courses by including more complex problems and aspects of gene expression, such as the excision of introns."
See: Decoding the Flu
Protein Synthesis Animation from Biology-Forums.com
Translation is the process of producing proteins from the mRNA. This YouTube video shows the molecular components involved in the process. It also animates how the peptide is elongated through interaction between mRNA, ribosome, tRNA, and residues. Protein Synthese Animation
The Central Dogma Animation by RIKEN Omics Science Center
The 'Central Dogma' of molecular biology is that 'DNA makes RNA makes protein'. This anime shows how molecular machines transcribe the genes in the DNA of every cell into portable RNA messages, how those messenger RNA are modified and exported from the nucleus, and finally how the RNA code is read to build proteins. Animation: The Central Dogma
A Prezi of this information can be found at: NHGRI Teacher Resouces-Central Dogma
Contributing Team of Educators:
Kari D. Loomis, Ph.D., Mars Hill College
Luisel Ricks, Ph.D., Howard University
Mark Bolt, Ph.D., University of Pikeville
Cathy Dobbs, Ph.D., Joliet Junior College
Changhui Yan, Ph.D., North Dakota State University
Solomon Adekunle, Ph.D., Southern University
In biology, transcription is the process of transcribing or making a copy of the genetic information stored in a DNA strand into a complementary strand of RNA (messenger RNA or mRNA) with the aid of RNA polymerases. In prokaryotes, the process occurs in the cytoplasm. In eukaryotes, it takes place inside the nucleus. The general steps of transcription are (1) initiation, (2) promoter escape, (3) elongation, and (4) termination. In brief, the RNA polymerase together with certain transcription factors binds to the DNA promoter. This causes the part of the DNA to unwind and form a transcription bubble. A site in the transcription bubble binds to the RNA polymerase. A phase of abortive cycles of short mRNA transcripts are produced and released. The RNA polymerase escapes the promoter to proceed to the elongation step where mRNA transcript is formed while traversing the noncoding strand of the DNA. In the last phase, the hydrogen bonds of the RNA-DNA helix break. In eukaryotes, the mRNA transcript goes through further processing. It goes through polyadenylation, capping, and splicing. After this, the mRNA transcript that carries a copy of the coding segment of the DNA is brought to the ribosomal site for translation.
Transcription is a biological process wherein a segment of the DNA is copied to mRNA. The general steps are initiation, promoter escape, elongation, and termination. During initiation, RNA polymerase binds to the promoter region of the DNA. A transcription bubble forms, opening the DNA strand and exposing a segment that will be transcribed. Abortive initiation causes the formation and the release of small RNA products. RNA polymerase, then, escapes the promoter. RNA polymerase adds RNA nucleotides as it traverses the DNA template. RNA sugar-phosphate backbone forms on the RNA strand. Finally, hydrogen bonds of the RNA-DNA helix break in order to release the newly synthesized mRNA transcript. In eukaryotes, post-transcriptional events (e.g. capping, polyadenylation, and splicing) ensue.
Transcription is a biological process wherein the mRNA transcript (i.e. a copy of the coding sequence for a particular protein) is produced, generally by transcribing the template strand of the DNA. This transcript serves as a template for the next step of protein biosynthesis, translation, through the help of the enzyme, RNA polymerase. Thus, transcription is regarded as the first step of gene expression and protein biosynthesis.
The term transcription came from Latin transcriptiōnem, from trānscrībō, meaning “transcribe”.
The central dogma of molecular biology holds that the genetic information flows from DNA to DNA through the replication and from DNA to mRNA through transcription. mRNA is translated (translation into a protein comprised of a specific sequence of amino acids. The sequence is determined by the sequence of trinucleotide codons. Each codon is a set of three adjacent nucleotides.
Transcription vs. replication
Both transcription and replication are biological processes of producing a copy of DNA. However, the output of replication is an exact copy of DNA whereas in transcription the output is not an exact copy but an mRNA transcript where thymines are replaced by uracils. In replication, the complementary base pairing includes the adenine-thymine (AT) and the guanine-cytosine (GC) base pairings. In transcription, base pairings are adenine-uracil (AU) and guanine-cytosine (GC). In replication, the enzyme involved is DNA polymerase whereas in transcription the enzyme is RNA polymerase. Both replication and transcription proceeds in the 5′ → 3′ direction. But unlike DNA replication, transcription needs no primer to initiate the process. In prokaryotes, both of them occur in the cytoplasm. In eukaryotes, both occur in the nucleus. While replication is a preparatory stage for cell division such as mitosis transcription is the initial stage of gene expression and protein synthesis.
Transcription vs. translation
Both transcription and translation are steps in protein biosynthesis. However, transcription occurs first before translation. Transcription produces mRNA that carries the code to be translated into a specific protein (or polypeptide). The code is a copy of the DNA coding segment. It specifies the specific sequence of amino acids. Thus, the flow of genetic information in transcription is from DNA → mRNA whereas in translation the flow is from mRNA → amino acid or protein. Both processes are assisted by enzymes: RNA polymerase assists in transcription whereas ribozyme in translation. In prokaryotes, transcription occurs in the cytoplasm whereas in eukaryotes it occurs in the nucleus. As for translation, it takes place in the cytoplasm where the ribosomes are located in both prokaryotic and eukaryotic cells.
RNA codon amino acid chart.
In biology, a codon refers to any of a set of three adjacent nucleotides that specify for a particular amino acid. For example, Guanine-Uracil-Uracil (GUU) codes for the amino acid valine. The Cytosine-Uracil-Adenine (CUA) codes for leucine. Uracil-Adenine-Adenine (UAA) is a stop codon. The codons of the mRNA complement the trinucleotides in the tRNA. The trinucleotides in the tRNA are called anticodons. For example, the Guanine-Guanine-Guanine (GGG) codon in the mRNA will complementary pair up with the Cytosine-Cytosine-Cytosine (CCC) anticodon of tRNA.
Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil (U) in all instances where thymine (T) would have occurred in a DNA complement. Also unlike DNA replication where DNA is synthesized, transcription does not involve an RNA primer to initiate RNA synthesis. The steps of transcription are as follows: (1) Initiation, (2) Promoter escape, (3) Elongation, and (4) Termination.
RNA polymerase, with the assistance of certain transcription factors, binds to the promoter of DNA, forming RNA polymerase-promoter closed complex. This is then followed by the opening (unwinding) of DNA at the promoter region, forming an open complex. The exposed portion of the DNA following the unwinding forms a transcription bubble. RNA polymerase, then, binds to a transcription start site in the transcription bubble. A phase of abortive initiation (cycles of synthesis) occurs resulting in the release of short mRNA transcripts (about 2 to 15 nucleotides).
The step after initiation is promoter escape. RNA polymerase escapes the promoter so that it can enter into the elongation step.
As RNA polymerase traverses the template noncoding strand of the DNA from 3′ → 5′, it facilitates nucleotide base pairing. Nucleotides of the mRNA are added from 5′ → 3′, producing a copy of the non-template coding strand of the DNA, except for the thymine (replaced by uracil). The sugar-phosphate backbone forms through RNA polymerase. Thus, the sugar component of the backbone is a ribose (as opposed to the sugar of DNA, which is a deoxyribose).
During this phase, hydrogen bonds of the RNA-DNA helix break. In eukaryotes, the mRNA transcript goes through further processing. It goes through polyadenylation, capping, and splicing. The termination mechanism employed by prokaryotes may either be rho-dependent or rho-independent. In eukaryotes, termination involves both the poly A signal and the downstream terminator sequence.
Prokaryotic transcription vs. eukaryotic transcription
In both prokaryotes and eukaryotes, the genetic flow in transcription is from DNA to RNA. Both use RNA polymerase to assist in the process. However, eukaryotes have three types of RNA polymerases (I, II, and III). Prokaryotes have only one type.
While transcription occurs in the cytoplasm of prokaryotes, it takes place in the nucleus of eukaryotes. If the RNA copy contains the coding segment of the DNA it leaves the nucleus as mRNA for translation at the ribosomal site. In bacteria, the mRNA does not undergo processing prior to translation. Thus, the bacterial mRNA lacks the cap and poly A tail. Conversely, in eukaryotes, the mRNA is further processed by the addition of a cap and a poly A tail and splicing prior to translation. Another major difference is that in bacteria transcription and translation can occur simultaneously. In eukaryotes, transcription has to be completed first before translation can proceed. The mRNA produced by prokaryotes is polycistronic, which means a single mRNA could contain more than one gene. In contrast, the mRNA of eukaryotes is monocistronic since a single mRNA can carry only one gene.
- Transcription factor
- Reverse transcription
- Transcription factor Sp4
- Transcription factor HES 1
- Oligodendrocyte transcription factor 1
References and further reading
- Prokaryotic vs. Eukaryotic Transcription. (2019). Retrieved from Uwec.edu website: https://www.chem.uwec.edu/webpapers2006/sites/demlba/folder/provseuk.html
- Central Dogma of Biology. (2014). Retrieved from Csbsju.edu website: http://employees.csbsju.edu/hjakubowski/classes/chem and society/cent-dogma/olcentdogma.html
- Translation: DNA to mRNA to Protein Learn Science at Scitable. (2013). Retrieved from Nature.com website: https://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393/
- Transcription and translation. (2017, April 26). Retrieved from Uq.edu.au website: https://di.uq.edu.au/community-and-alumni/sparq-ed/sparq-ed-services/transcription-and-translation
- Transcription / Translation. (2019). Retrieved from Iupui.edu website: https://www.biology.iupui.edu/biocourses/N100/2k3ch13dogma.html
- Protein Synthesis. (2019). Retrieved from Elmhurst.edu website: http://chemistry.elmhurst.edu/vchembook/584proteinsyn.html
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Last updated on July 21st, 2021
Transcription is the process by which the information in a strand of DNA is copied into a new molecule of messenger RNA (mRNA). DNA safely and stably stores genetic material in the nuclei of cells as a reference, or template. Meanwhile, mRNA is comparable to a copy from a reference book because it carries the same information as DNA but is not used for long-term storage and can freely exit the nucleus. Although the mRNA contains the same information, it is not an identical copy of the DNA segment, because its sequence is complementary to the DNA template.Transcription is carried out by an enzyme called RNA polymerase and a number of accessory proteins called transcription factors. Transcription factors can bind to specific DNA sequences called enhancer and promoter sequences in order to recruit RNA polymerase to an appropriate transcription site. Together, the transcription factors and RNA polymerase form a complex called the transcription initiation complex. This complex initiates transcription, and the RNA polymerase begins mRNA synthesis by matching complementary bases to the original DNA strand. The mRNA molecule is elongated and, once the strand is completely synthesized, transcription is terminated. The newly formed mRNA copies of the gene then serve as blueprints for protein synthesis during the process of translation.
Definition biology transcription
This article is about transcription in biology. For other uses, see Transcription.
Process of copying a segment of DNA into RNA
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). Averaged over multiple cell types in a given tissue, the quantity of mRNA is more than 10 times the quantity of ncRNA (though in particular single cell types ncRNAs may exceed mRNAs). The general preponderance of mRNA in cells is valid even though less than 2% of the human genome can be transcribed into mRNA (Human genome#Coding vs. noncoding DNA), while at least 80% of mammalian genomic DNA can be actively transcribed (in one or more types of cells), with the majority of this 80% considered to be ncRNA.
Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript.
Transcription proceeds in the following general steps:
- RNA polymerase, together with one or more general transcription factors, binds to promoter DNA.
- RNA polymerase generates a transcription bubble, which separates the two strands of the DNA helix. This is done by breaking the hydrogen bonds between complementary DNA nucleotides.
- RNA polymerase adds RNA nucleotides (which are complementary to the nucleotides of one DNA strand).
- RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand.
- Hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand.
- If the cell has a nucleus, the RNA may be further processed. This may include polyadenylation, capping, and splicing.
- The RNA may remain in the nucleus or exit to the cytoplasm through the nuclear pore complex.
If the stretch of DNA is transcribed into an RNA molecule that encodes a protein, the RNA is termed messenger RNA (mRNA); the mRNA, in turn, serves as a template for the protein's synthesis through translation. Other stretches of DNA may be transcribed into small non-coding RNAs such as microRNA, transfer RNA (tRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), or enzymatic RNA molecules called ribozymes as well as larger non-coding RNAs such as ribosomal RNA (rRNA), and long non-coding RNA (lncRNA). Overall, RNA helps synthesize, regulate, and process proteins; it therefore plays a fundamental role in performing functions within a cell.
In virology, the term transcription may also be used when referring to mRNA synthesis from an RNA molecule (i.e., equivalent to RNA replication). For instance, the genome of a negative-sense single-stranded RNA (ssRNA -) virus may be a template for a positive-sense single-stranded RNA (ssRNA +)[clarification needed]. This is because the positive-sense strand contains the sequence information needed to translate the viral proteins needed for viral replication. This process is catalyzed by a viral RNA replicase.[clarification needed]
A DNA transcription unit encoding for a protein may contain both a coding sequence, which will be translated into the protein, and regulatory sequences, which direct and regulate the synthesis of that protein. The regulatory sequence before ("upstream" from) the coding sequence is called the five prime untranslated region (5'UTR); the sequence after ("downstream" from) the coding sequence is called the three prime untranslated region (3'UTR).
As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil (U) in all instances where thymine (T) would have occurred in a DNA complement.
Only one of the two DNA strands serve as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3' end to the 5' end during transcription (3' → 5'). The complementary RNA is created in the opposite direction, in the 5' → 3' direction, matching the sequence of the sense strand with the exception of switching uracil for thymine. This directionality is because RNA polymerase can only add nucleotides to the 3' end of the growing mRNA chain. This use of only the 3' → 5' DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This also removes the need for an RNA primer to initiate RNA synthesis, as is the case in DNA replication.
The non-template (sense) strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript (except for the substitution of uracil for thymine). This is the strand that is used by convention when presenting a DNA sequence.
Transcription has some proofreading mechanisms, but they are fewer and less effective than the controls for copying DNA. As a result, transcription has a lower copying fidelity than DNA replication.
Further information: Bacterial transcription and Eukaryotic transcription
Transcription is divided into initiation, promoter escape, elongation, and termination.
Setting up for transcription
Enhancers, transcription factors, Mediator complex and DNA loops in mammalian transcription
Setting up for transcription in mammals is regulated by many cis-regulatory elements, including core promoter and promoter-proximal elements that are located near the transcription start sites of genes. Core promoters combined with general transcription factors are sufficient to direct transcription initiation, but generally have low basal activity. Other important cis-regulatory modules are localized in DNA regions that are distant from the transcription start sites. These include enhancers, silencers, insulators and tethering elements. Among this constellation of elements, enhancers and their associated transcription factors have a leading role in the initiation of gene transcription. An enhancer localized in a DNA region distant from the promoter of a gene can have a very large effect on gene transcription, with some genes undergoing up to 100-fold increased transcription due to an activated enhancer.
Enhancers are regions of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene transcription programs, most often by looping through long distances to come in physical proximity with the promoters of their target genes. While there are hundreds of thousands of enhancer DNA regions, for a particular type of tissue only specific enhancers are brought into proximity with the promoters that they regulate. In a study of brain cortical neurons, 24,937 loops were found, bringing enhancers to their target promoters. Multiple enhancers, each often at tens or hundred of thousands of nucleotides distant from their target genes, loop to their target gene promoters and can coordinate with each other to control transcription of their common target gene.
The schematic illustration in this section shows an enhancer looping around to come into close physical proximity with the promoter of a target gene. The loop is stabilized by a dimer of a connector protein (e.g. dimer of CTCF or YY1), with one member of the dimer anchored to its binding motif on the enhancer and the other member anchored to its binding motif on the promoter (represented by the red zigzags in the illustration). Several cell function specific transcription factors (there are about 1,600 transcription factors in a human cell) generally bind to specific motifs on an enhancer and a small combination of these enhancer-bound transcription factors, when brought close to a promoter by a DNA loop, govern level of transcription of the target gene. Mediator (a complex usually consisting of about 26 proteins in an interacting structure) communicates regulatory signals from enhancer DNA-bound transcription factors directly to the RNA polymerase II (pol II) enzyme bound to the promoter.
Enhancers, when active, are generally transcribed from both strands of DNA with RNA polymerases acting in two different directions, producing two enhancer RNAs (eRNAs) as illustrated in the Figure. An inactive enhancer may be bound by an inactive transcription factor. Phosphorylation of the transcription factor may activate it and that activated transcription factor may then activate the enhancer to which it is bound (see small red star representing phosphorylation of transcription factor bound to enhancer in the illustration). An activated enhancer begins transcription of its RNA before activating transcription of messenger RNA from its target gene.
CpG island methylation and demethylation
Transcription regulation at about 60% of promoters is also controlled by methylation of cytosines within CpG dinucleotides (where 5’ cytosine is followed by 3’ guanine or CpG sites). 5-methylcytosine (5-mC) is a methylated form of the DNA base cytosine (see Figure). 5-mC is an epigenetic marker found predominantly within CpG sites. About 28 million CpG dinucleotides occur in the human genome. In most tissues of mammals, on average, 70% to 80% of CpG cytosines are methylated (forming 5-methylCpG or 5-mCpG).  Methylated cytosines within 5’cytosine-guanine 3’ sequences often occur in groups, called CpG islands. About 60% of promoter sequences have a CpG island while only about 6% of enhancer sequences have a CpG island. CpG islands constitute regulatory sequences, since if CpG islands are methylated in the promoter of a gene this can reduce or silence gene transcription.
DNA methylation regulates gene transcription through interaction with methyl binding domain (MBD) proteins, such as MeCP2, MBD1 and MBD2. These MBD proteins bind most strongly to highly methylated CpG islands. These MBD proteins have both a methyl-CpG-binding domain as well as a transcription repression domain. They bind to methylated DNA and guide or direct protein complexes with chromatin remodeling and/or histone modifying activity to methylated CpG islands. MBD proteins generally repress local chromatin such as by catalyzing the introduction of repressive histone marks, or creating an overall repressive chromatin environment through nucleosome remodeling and chromatin reorganization.
As noted in the previous section, transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a gene. The binding sequence for a transcription factor in DNA is usually about 10 or 11 nucleotides long. As summarized in 2009, Vaquerizas et al. indicated there are approximately 1,400 different transcription factors encoded in the human genome by genes that constitute about 6% of all human protein encoding genes. About 94% of transcription factor binding sites (TFBSs) that are associated with signal-responsive genes occur in enhancers while only about 6% of such TFBSs occur in promoters.
EGR1 protein is a particular transcription factor that is important for regulation of methylation of CpG islands. An EGR1 transcription factor binding site is frequently located in enhancer or promoter sequences. There are about 12,000 binding sites for EGR1 in the mammalian genome and about half of EGR1 binding sites are located in promoters and half in enhancers. The binding of EGR1 to its target DNA binding site is insensitive to cytosine methylation in the DNA.
While only small amounts of EGR1 transcription factor protein are detectable in cells that are un-stimulated, translation of the EGR1 gene into protein at one hour after stimulation is drastically elevated. Expression of EGR1 transcription factor proteins, in various types of cells, can be stimulated by growth factors, neurotransmitters, hormones, stress and injury. In the brain, when neurons are activated, EGR1 proteins are up-regulated and they bind to (recruit) the pre-existing TET1 enzymes which are highly expressed in neurons. TET enzymes can catalyse demethylation of 5-methylcytosine. When EGR1 transcription factors bring TET1 enzymes to EGR1 binding sites in promoters, the TET enzymes can demethylate the methylated CpG islands at those promoters. Upon demethylation, these promoters can then initiate transcription of their target genes. Hundreds of genes in neurons are differentially expressed after neuron activation through EGR1 recruitment of TET1 to methylated regulatory sequences in their promoters.
The methylation of promoters is also altered in response to signals. The three mammalian DNA methyltransferasess (DNMT1, DNMT3A, and DNMT3B) catalyze the addition of methyl groups to cytosines in DNA. While DNMT1 is a “maintenance” methyltransferase, DNMT3A and DNMT3B can carry out new methylations. There are also two spliceprotein isoforms produced from the DNMT3A gene: DNA methyltransferase proteins DNMT3A1 and DNMT3A2.
The splice isoform DNMT3A2 behaves like the product of a classical immediate-early gene and, for instance, it is robustly and transiently produced after neuronal activation. Where the DNA methyltransferase isoform DNMT3A2 binds and adds methyl groups to cytosines appears to be determined by histone post translational modifications.
On the other hand, neural activation causes degradation of DNMT3A1 accompanied by reduced methylation of at least one evaluated targeted promoter.
Transcription begins with the binding of RNA polymerase, together with one or more general transcription factors, to a specific DNA sequence referred to as a "promoter" to form an RNA polymerase-promoter "closed complex". In the "closed complex" the promoter DNA is still fully double-stranded.
RNA polymerase, assisted by one or more general transcription factors, then unwinds approximately 14 base pairs of DNA to form an RNA polymerase-promoter "open complex". In the "open complex" the promoter DNA is partly unwound and single-stranded. The exposed, single-stranded DNA is referred to as the "transcription bubble."
RNA polymerase, assisted by one or more general transcription factors, then selects a transcription start site in the transcription bubble, binds to an initiating NTP and an extending NTP (or a short RNA primer and an extending NTP) complementary to the transcription start site sequence, and catalyzes bond formation to yield an initial RNA product.
In bacteria, RNA polymerase holoenzyme consists of five subunits: 2 α subunits, 1 β subunit, 1 β' subunit, and 1 ω subunit. In bacteria, there is one general RNA transcription factor known as a sigma factor. RNA polymerase core enzyme binds to the bacterial general transcription (sigma) factor to form RNA polymerase holoenzyme and then binds to a promoter. (RNA polymerase is called a holoenzyme when sigma subunit is attached to the core enzyme which is consist of 2 α subunits, 1 β subunit, 1 β' subunit only). Unlike eukaryotes, the initiating nucleotide of nascent bacterial mRNA is not capped with a modified guanine nucleotide. The initiating nucleotide of bacterial transcripts bears a 5′ triphosphate (5′-PPP), which can be used for genome-wide mapping of transcription initiation sites.
In archaea and eukaryotes, RNA polymerase contains subunits homologous to each of the five RNA polymerase subunits in bacteria and also contains additional subunits. In archaea and eukaryotes, the functions of the bacterial general transcription factor sigma are performed by multiple general transcription factors that work together. In archaea, there are three general transcription factors: TBP, TFB, and TFE. In eukaryotes, in RNA polymerase II-dependent transcription, there are six general transcription factors: TFIIA, TFIIB (an ortholog of archaeal TFB), TFIID (a multisubunit factor in which the key subunit, TBP, is an ortholog of archaeal TBP), TFIIE (an ortholog of archaeal TFE), TFIIF, and TFIIH. The TFIID is the first component to bind to DNA due to binding of TBP, while TFIIH is the last component to be recruited. In archaea and eukaryotes, the RNA polymerase-promoter closed complex is usually referred to as the "preinitiation complex."
Transcription initiation is regulated by additional proteins, known as activators and repressors, and, in some cases, associated coactivators or corepressors, which modulate formation and function of the transcription initiation complex.
After the first bond is synthesized, the RNA polymerase must escape the promoter. During this time there is a tendency to release the RNA transcript and produce truncated transcripts. This is called abortive initiation, and is common for both eukaryotes and prokaryotes. Abortive initiation continues to occur until an RNA product of a threshold length of approximately 10 nucleotides is synthesized, at which point promoter escape occurs and a transcription elongation complex is formed.
Mechanistically, promoter escape occurs through DNA scrunching, providing the energy needed to break interactions between RNA polymerase holoenzyme and the promoter.
In bacteria, it was historically thought that the sigma factor is definitely released after promoter clearance occurs. This theory had been known as the obligate release model. However, later data showed that upon and following promoter clearance, the sigma factor is released according to a stochastic model known as the stochastic release model.
In eukaryotes, at an RNA polymerase II-dependent promoter, upon promoter clearance, TFIIH phosphorylates serine 5 on the carboxy terminal domain of RNA polymerase II, leading to the recruitment of capping enzyme (CE). The exact mechanism of how CE induces promoter clearance in eukaryotes is not yet known.
One strand of the DNA, the template strand (or noncoding strand), is used as a template for RNA synthesis. As transcription proceeds, RNA polymerase traverses the template strand and uses base pairing complementarity with the DNA template to create an RNA copy (which elongates during the traversal). Although RNA polymerase traverses the template strand from 3' → 5', the coding (non-template) strand and newly formed RNA can also be used as reference points, so transcription can be described as occurring 5' → 3'. This produces an RNA molecule from 5' → 3', an exact copy of the coding strand (except that thymines are replaced with uracils, and the nucleotides are composed of a ribose (5-carbon) sugar where DNA has deoxyribose (one fewer oxygen atom) in its sugar-phosphate backbone).
mRNA transcription can involve multiple RNA polymerases on a single DNA template and multiple rounds of transcription (amplification of particular mRNA), so many mRNA molecules can be rapidly produced from a single copy of a gene. The characteristic elongation rates in prokaryotes and eukaryotes are about 10-100 nts/sec. In eukaryotes, however, nucleosomes act as major barriers to transcribing polymerases during transcription elongation. In these organisms, the pausing induced by nucleosomes can be regulated by transcription elongation factors such as TFIIS.
Elongation also involves a proofreading mechanism that can replace incorrectly incorporated bases. In eukaryotes, this may correspond with short pauses during transcription that allow appropriate RNA editing factors to bind. These pauses may be intrinsic to the RNA polymerase or due to chromatin structure.
Main article: Terminator (genetics)
Bacteria use two different strategies for transcription termination – Rho-independent termination and Rho-dependent termination. In Rho-independent transcription termination, RNA transcription stops when the newly synthesized RNA molecule forms a G-C-rich hairpin loop followed by a run of Us. When the hairpin forms, the mechanical stress breaks the weak rU-dA bonds, now filling the DNA–RNA hybrid. This pulls the poly-U transcript out of the active site of the RNA polymerase, terminating transcription. In the "Rho-dependent" type of termination, a protein factor called "Rho" destabilizes the interaction between the template and the mRNA, thus releasing the newly synthesized mRNA from the elongation complex.
Transcription termination in eukaryotes is less well understood than in bacteria, but involves cleavage of the new transcript followed by template-independent addition of adenines at its new 3' end, in a process called polyadenylation.
Role of RNA Polymerase in Post-Transcriptional changes in RNA
RNA polymerase plays a very crucial role in all steps including post-transcriptional changes in RNA.
As shown in the image in the right it is evident that the CTD (C Terminal Domain) is a tail that changes its shape; this tail will be used as a carrier of splicing, capping and polyadenylation, as shown in the image on the left.
Transcription inhibitors can be used as antibiotics against, for example, pathogenic bacteria (antibacterials) and fungi (antifungals). An example of such an antibacterial is rifampicin, which inhibits bacterial transcription of DNA into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit, while 8-hydroxyquinoline is an antifungal transcription inhibitor. The effects of histone methylation may also work to inhibit the action of transcription. Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of the XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.
Main article: Regulation of transcription in cancer
In vertebrates, the majority of gene promoters contain a CpG island with numerous CpG sites. When many of a gene's promoter CpG sites are methylated the gene becomes inhibited (silenced). Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, transcriptional inhibition (silencing) may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally inhibited by CpG island methylation (see regulation of transcription in cancer). Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs. In breast cancer, transcriptional repression of BRCA1 may occur more frequently by over-expressed microRNA-182 than by hypermethylation of the BRCA1 promoter (see Low expression of BRCA1 in breast and ovarian cancers).
Main article: Transcription factories
Active transcription units are clustered in the nucleus, in discrete sites called transcription factories or euchromatin. Such sites can be visualized by allowing engaged polymerases to extend their transcripts in tagged precursors (Br-UTP or Br-U) and immuno-labeling the tagged nascent RNA. Transcription factories can also be localized using fluorescence in situ hybridization or marked by antibodies directed against polymerases. There are ~10,000 factories in the nucleoplasm of a HeLa cell, among which are ~8,000 polymerase II factories and ~2,000 polymerase III factories. Each polymerase II factory contains ~8 polymerases. As most active transcription units are associated with only one polymerase, each factory usually contains ~8 different transcription units. These units might be associated through promoters and/or enhancers, with loops forming a "cloud" around the factor.
A molecule that allows the genetic material to be realized as a protein was first hypothesized by François Jacob and Jacques Monod. Severo Ochoa won a Nobel Prize in Physiology or Medicine in 1959 for developing a process for synthesizing RNA in vitro with polynucleotide phosphorylase, which was useful for cracking the genetic code. RNA synthesis by RNA polymerase was established in vitro by several laboratories by 1965; however, the RNA synthesized by these enzymes had properties that suggested the existence of an additional factor needed to terminate transcription correctly.
In 1972, Walter Fiers became the first person to actually prove the existence of the terminating enzyme.
Roger D. Kornberg won the 2006 Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription".
Measuring and detecting
Transcription can be measured and detected in a variety of ways:
- G-Less Cassette transcription assay: measures promoter strength
- Run-off transcription assay: identifies transcription start sites (TSS)
- Nuclear run-on assay: measures the relative abundance of newly formed transcripts
- KAS-seq: measures single-stranded DNA generated by RNA polymerases; can work with 1,000 cells.
- RNase protection assay and ChIP-Chip of RNAP: detect active transcription sites
- RT-PCR: measures the absolute abundance of total or nuclear RNA levels, which may however differ from transcription rates
- DNA microarrays: measures the relative abundance of the global total or nuclear RNA levels; however, these may differ from transcription rates
- In situ hybridization: detects the presence of a transcript
- MS2 tagging: by incorporating RNA stem loops, such as MS2, into a gene, these become incorporated into newly synthesized RNA. The stem loops can then be detected using a fusion of GFP and the MS2 coat protein, which has a high affinity, sequence-specific interaction with the MS2 stem loops. The recruitment of GFP to the site of transcription is visualized as a single fluorescent spot. This new approach has revealed that transcription occurs in discontinuous bursts, or pulses (see Transcriptional bursting). With the notable exception of in situ techniques, most other methods provide cell population averages, and are not capable of detecting this fundamental property of genes.
- Northern blot: the traditional method, and until the advent of RNA-Seq, the most quantitative
- RNA-Seq: applies next-generation sequencing techniques to sequence whole transcriptomes, which allows the measurement of relative abundance of RNA, as well as the detection of additional variations such as fusion genes, post-transcriptional edits and novel splice sites
- Single cell RNA-Seq: amplifies and reads partial transcriptomes from isolated cells, allowing for detailed analyses of RNA in tissues, embryos, and cancers
Main article: Reverse transcription
Some viruses (such as HIV, the cause of AIDS), have the ability to transcribe RNA into DNA. HIV has an RNA genome that is reverse transcribed into DNA. The resulting DNA can be merged with the DNA genome of the host cell. The main enzyme responsible for synthesis of DNA from an RNA template is called reverse transcriptase.
In the case of HIV, reverse transcriptase is responsible for synthesizing a complementary DNA strand (cDNA) to the viral RNA genome. The enzyme ribonuclease H then digests the RNA strand, and reverse transcriptase synthesises a complementary strand of DNA to form a double helix DNA structure ("cDNA"). The cDNA is integrated into the host cell's genome by the enzyme integrase, which causes the host cell to generate viral proteins that reassemble into new viral particles. In HIV, subsequent to this, the host cell undergoes programmed cell death, or apoptosis of T cells. However, in other retroviruses, the host cell remains intact as the virus buds out of the cell.
Some eukaryotic cells contain an enzyme with reverse transcription activity called telomerase. Telomerase is a reverse transcriptase that lengthens the ends of linear chromosomes. Telomerase carries an RNA template from which it synthesizes a repeating sequence of DNA, or "junk" DNA. This repeated sequence of DNA is called a telomere and can be thought of as a "cap" for a chromosome. It is important because every time a linear chromosome is duplicated, it is shortened. With this "junk" DNA or "cap" at the ends of chromosomes, the shortening eliminates some of the non-essential, repeated sequence rather than the protein-encoding DNA sequence, that is farther away from the chromosome end.
Telomerase is often activated in cancer cells to enable cancer cells to duplicate their genomes indefinitely without losing important protein-coding DNA sequence. Activation of telomerase could be part of the process that allows cancer cells to become immortal. The immortalizing factor of cancer via telomere lengthening due to telomerase has been proven to occur in 90% of all carcinogenic tumors in vivo with the remaining 10% using an alternative telomere maintenance route called ALT or Alternative Lengthening of Telomeres.
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After the day before yesterday by the fire, do you have something to hide under your swimsuit. Slyly asked Lyudka, incredibly embarrassing with such a question Nyusha. What are you going to swim naked with the boys. Nyusha asked timidly.