Journal Article

Getting up to speed with transcription elongation by RNA polymerase II

Jonkers, Iris, Lis, John T.

2015

Overview

Key Points RNA polymerase II (Pol II) elongation is a highly regulated process. Regulation of transcription is often mediated at the level of promoter-proximal pausing of Pol II, in which Pol II is paused approximately 30–60 nucleotides downstream of the transcription start site (TSS) and awaits recruitment of kinase positive transcription elongation factor-b (P-TEFb). P-TEFb is the main factor required to release paused Pol II from the promoter-proximal region, and can directly or indirectly be recruited by many factors, including bromodomain-containing protein 4 (BRD4) and the super elongation complex (SEC). Elongation rates throughout the gene body are not uniform but vary between, and within genes, and can range from ∼1 to 6 kb per minute. Transient slowdown of Pol II is observed up to 15 kb downstream of the TSS, at exons and near the poly(A) cleavage site. Elongation rates can affect co-transcriptional RNA processes such as splicing and termination, as well as genome stability. Pausing of RNA polymerase II (Pol II) in promoter-proximal regions and its release to initiate productive elongation are key steps in the regulation of transcription, and involve many factors. Evidence is now emerging that transcriptional elongation is highly dynamic. Elongation rates vary between genes and across the length of a gene, affecting splicing, termination and genome stability. Recent advances in sequencing techniques that measure nascent transcripts and that reveal the positioning of RNA polymerase II (Pol II) have shown that the pausing of Pol II in promoter-proximal regions and its release to initiate a phase of productive elongation are key steps in transcription regulation. Moreover, after the release of Pol II from the promoter-proximal region, elongation rates are highly dynamic throughout the transcription of a gene, and vary on a gene-by-gene basis. Interestingly, Pol II elongation rates affect co-transcriptional processes such as splicing, termination and genome stability. Increasing numbers of factors and regulatory mechanisms have been associated with the steps of transcription elongation by Pol II, revealing that elongation is a highly complex process. Elongation is thus now recognized as a key phase in the regulation of transcription by Pol II.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/2019 / 631/337/572 / Animals / Antineoplastic Agents - therapeutic use / Biochemistry / Cancer Research / Cell Biology / Cell Cycle Proteins / Developmental Biology / Drosophila melanogaster - genetics / Drosophila melanogaster - metabolism / Drosophila Proteins - antagonists & inhibitors / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Genetic research / Genetic transcription / Genome / Genomic Instability / Humans / Life Sciences / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - pathology / Nuclear Proteins - antagonists & inhibitors / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / Positive Transcriptional Elongation Factor B - antagonists & inhibitors / Positive Transcriptional Elongation Factor B - genetics / Positive Transcriptional Elongation Factor B - metabolism / Promoter Regions, Genetic / Properties / Protein Binding / review-article / RNA Polymerase II - genetics / RNA Polymerase II - metabolism / RNA polymerases / Stem Cells / Transcription Elongation, Genetic / Transcription Factors - antagonists & inhibitors / Transcription Factors - genetics / Transcription Factors - metabolism / Translation elongation factors