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Review
. 2017 Jun:46:72-80.
doi: 10.1016/j.ceb.2017.03.002. Epub 2017 Mar 28.

Pause & go: from the discovery of RNA polymerase pausing to its functional implications

Andreas Mayer  1 , Heather M Landry  1 , L Stirling Churchman  2
Affiliations
Review

Pause & go: from the discovery of RNA polymerase pausing to its functional implications

Andreas Mayer et al. Curr Opin Cell Biol. 2017 Jun.

Abstract

The synthesis of nascent RNA is a discontinuous process in which phases of productive elongation by RNA polymerase are interrupted by frequent pauses. Transcriptional pausing was first observed decades ago, but was long considered to be a special feature of transcription at certain genes. This view was challenged when studies using genome-wide approaches revealed that RNA polymerase II pauses at promoter-proximal regions in large sets of genes in Drosophila and mammalian cells. High-resolution genomic methods uncovered that pausing is not restricted to promoters, but occurs globally throughout gene-body regions, implying the existence of key-rate limiting steps in nascent RNA synthesis downstream of transcription initiation. Here, we outline the experimental breakthroughs that led to the discovery of pervasive transcriptional pausing, discuss its emerging roles and regulation, and highlight the importance of pausing in human development and disease.

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Figures

Figure 1
Figure 1. RNA polymerase II pausing during the gene transcription cycle
(A) Different transcriptional states of RNA polymerase II (Pol II) during distinct phases of the gene transcription cycle: pre-initiation/initiation, elongation, and termination. Pol II is shown in purple; nascent RNA is in green with the 3′-end nucleotide labeled in red; double-stranded DNA is indicated by two black lines; TSS: transcription start site; pA: polyadenylation site. (B) Pol II pausing with single-nucleotide resolution at the promoter-proximal (left panel) and gene-body regions (right panel) as revealed by human NET-seq (Box 1). NET-seq data obtained from HeLa S3 cells are shown for the representative HNRNPH1 gene[57]. Exonic and intronic regions are indicated by black boxes and black lines, respectively. TSS: transcription start site.
Figure 2
Figure 2
Milestones on the road to the discovery of pervasive transcriptional pausing
See this image and copyright information in PMC

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