What does transcription start with

Transcription occurs in the three steps—initiation, elongation, and termination—all shown here. Initiation is the beginning of transcription. It occurs when the enzyme RNA polymerase binds to a region of a gene called the promoter.

The enzyme is now ready to make a strand of mRNA with a complementary sequence of bases. Elongation is the addition of nucleotides to the mRNA strand. Termination is the ending of transcription, and occurs when RNA polymerase crosses a stop termination sequence in the gene. This video provides a review of these steps. You can stop watching the video at Transcription of eukaryotic genes by polymerases I and III is initiated in a similar manner, but the promoter sequences and transcriptional activator proteins vary.

In eukaryotes, termination of transcription occurs by different processes, depending upon the exact polymerase utilized. For pol I genes, transcription is stopped using a termination factor, through a mechanism similar to rho-dependent termination in bacteria. Transcription of pol III genes ends after transcribing a termination sequence that includes a polyuracil stretch, by a mechanism resembling rho-independent prokaryotic termination. Termination of pol II transcripts, however, is more complex.

Transcription of pol II genes can continue for hundreds or even thousands of nucleotides beyond the end of a noncoding sequence. The RNA strand is then cleaved by a complex that appears to associate with the polymerase.

Cleavage seems to be coupled with termination of transcription and occurs at a consensus sequence. Both polyadenylation and termination make use of the same consensus sequence, and the interdependence of the processes was demonstrated in the late s by work from several groups.

One group of scientists working with mouse globin genes showed that introducing mutations into the consensus sequence AATAAA, known to be necessary for poly A addition, inhibited both polyadenylation and transcription termination.

They measured the extent of termination by hybridizing transcripts with the different poly A consensus sequence mutants with wild-type transcripts, and they were able to see a decrease in the signal of hybridization , suggesting that proper termination was inhibited.

They therefore concluded that polyadenylation was necessary for termination Logan et. Another group obtained similar results using a monkey viral system, SV40 simian virus The exact relationship between cleavage and termination remains to be determined.

One model supposes that cleavage itself triggers termination; another proposes that polymerase activity is affected when passing through the consensus sequence at the cleavage site, perhaps through changes in associated transcriptional activation factors. Thus, research in the area of prokaryotic and eukaryotic transcription is still focused on unraveling the molecular details of this complex process, data that will allow us to better understand how genes are transcribed and silenced.

Connelly, S. Genes and Development 4 , — Dennis, P. Journal of Molecular Biology 84 , — Nature , — doi Izban, M. Journal of Biological Chemistry , — Kritikou, E.

Transcription elongation and termination: It ain't over until the polymerase falls off. Nature Milestones in Gene Expression 8 Lee, J. Methods in Molecular Biology , 23—37 Logan, J. A poly A addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene.

Proceedings of the National Academy of Sciences 23 , — Nabavi, S. Restriction Enzymes. Genetic Mutation. Functions and Utility of Alu Jumping Genes. Transposons: The Jumping Genes. DNA Transcription. What is a Gene? Colinearity and Transcription Units. Copy Number Variation. Copy Number Variation and Genetic Disease. Copy Number Variation and Human Disease.

Tandem Repeats and Morphological Variation. Chemical Structure of RNA. Eukaryotic Genome Complexity. RNA Functions. Citation: Clancy, S. Nature Education 1 1 In both cases, the 5' ends of these small RNAs are modified by the addition of the cap, a modification known to protect RNAs against degradation [ 24 ], and this is inconsistent with their being mere degradation products on a path to complete removal from the cell.

Over the past few years, unbiased transcriptional surveys have revealed that a large fraction of the genome can be detected as stable transcripts [ 1 , 2 , 4 ]. However, these experiments, often microarray-based, typically avoided interrogating the repetitive element fraction of genomes as hybridization signals could not be assigned to a unique region.

The advent of next-generation sequencing has made it possible to uniquely assign an RNA sequence to a particular repetitive element as long as there is some divergence from other copies of the element in the genome. Faulkner et al. Transcription within repetitive elements, specifically within retrotransposons, is apparently driven by their own promoters, which are surprisingly different from those previously characterized for these elements, and is highly tissue- and condition-specific.

The big question raised by this study is whether the large contribution of repetitive elements, and retrotransposons in particular, to a cell's transcriptome translates into a major influence on its phenotype. In this respect, an important aspect of the study of Faulkner et al. In fact, 15, in mouse and , in human of the putative novel TSSs within retrotransposons were identified as being associated with protein-coding transcripts, and the activity of mouse and human putative retrotransposon promoters was confirmed from existing expressed sequence tag EST data.

Also, when Faulkner et al. Taken together, these results show that repetitive elements could in fact drive the production of a wide array of novel isoforms of protein-coding genes whose regulation and coding potential could be different from the isoforms annotated so far.

It will be interesting to see how many of these putative protein-coding transcripts initiating within repetitive elements are actually translated. This question could be phrased as part of a more general question: what is the complexity of polypeptides made in human cells, given the apparently high transcriptional complexity of RNAs made from a protein-coding locus?

Analysis of available EST data has shown that, on average, a protein-coding locus can produce 5. It is not known, however, what fraction of these novel transcripts is actually translated and what fraction of such novel proteins would be functional.

Precise knowledge of the TSSs used in a given biological condition is indispensable for understanding how that transcription is regulated. The authors used information on the genomic positions of the regulatory regions for each transcript and changes in transcript copy number during differentiation.

For each promoter, known motifs for transcription factor binding sites were identified and this information was linked to changes in expression levels of the downstream transcript to infer the activity of the relevant transcription factors. From this, the authors identified 30 motifs whose activity explained most of the observed variation in gene expression; many of these motifs correspond to known regulators of the differentiation of macrophages - the particular cell type under study. The main conclusion reached is that a large number of different transcriptional regulators are required for differentiation, as opposed to the model in which the process is controlled by a small number of 'master regulators'.

A similar strategy could be applied to identify transcription factors involved in regulation of other developmental or disease systems. The information on the expression levels of transcripts linked to individual TSSs is particularly important, as the study described above [ 11 ] shows that empirical mapping of TSSs can explain expression data better than existing annotated TSSs can.

A caveat that must, however, be applied to techniques that use an RNA cap to identify TSSs, is the recent discovery that CAGE tags could represent 5' ends of RNAs generated by cleavage and subsequent re-capping [ 18 ], and that cytoplasmic enzyme complexes can add caps to 5'-monophosphate RNA molecules generated by ribonuclease cleavage [ 26 ]. This means that mere knowledge of the position of a capped nucleotide is not sufficient to define a TSS.

Additional information, such as the distribution of putative initiation sites within a promoter region [ 27 ], chromatin hallmarks associated with active promotors, the presence of RNA polymerase II initiation complexes and transcription factors [ 2 , 28 ] and appropriate sequence content [ 29 ], will be required to prove that a true initiation site has been identified and to re-evaluate the number of TSSs in human and other genomes. Curr Opin Cell Biol.

Article Google Scholar. Nat Rev Genet. Nat Methods. Genome Res. Nat Genet. Google Scholar.