Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans

By K. Adelman, J. Lis. Nature reviews genetics, 2012

1,170 citations recorded by the source corpus.

Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. Current data indicate that pausing is particularly enriched at genes in signal-responsive pathways. Here the evidence for pausing of Pol II from recent high-throughput studies will be discussed, as well as the potential interconnected functions of promoter-proximally paused Pol II.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ba420ed0d0fbc75af2cb963f81c8ec542790edd1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

The mechanisms behind the therapeutic activity of BET bromodomain inhibition (2014, background): “One such mechanism is through interactions with regulatory factors DSIF and NELF, which can maintain Pol II in a reversibly paused state (Adelman and Lis, 2012).”
Transcriptional Regulation and its Misregulation in Disease (2013, neutral): “Once the recruited RNA polymerase II molecules initiate transcription, they generally transcribe a short distance, typically 20–50bp, and then pause (Figure 1) (Adelman and Lis, 2012).”
Gene regulation by the act of long non-coding RNA transcription (2013, background): “This mechanism should not be confused with the phenomenon of genome-wide RNAPII pausing at promoters, which represents an intermediate step between RNAPII initiation and elongation phases and might be a common mechanism regulating differential gene expression in metazoans [84,85].”
Parsing the interferon transcriptional network and its disease associations (2016, positive): “In addition, transcriptional elongation may be facilitated: in several systems of rapidly inducible responses, transcripts are initiated at baseline; however, Pol-II is blocked by elongation inhibitory factors, and the activating signal relieves this block (Adelman and Lis, 2012).”
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes (2017, background): “For example, PARP-1 ADP-ribosylates NELF-A andNELF-E of negative elongation factor (NELF), a regulatory complex that promotes promoter-proximal pausing of RNA polymerase II (Adelman and Lis 2012).”
Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III (2020, background): “Pol I, Pol II, and Pol III are three distinct DNAdependent RNA polymerases that function together with thousands of transcriptional and chromatin regulators to synthesize rRNA, mRNA, and tRNA, respectively [9, 30-36].”
Gene Ontology annotation of sequence-specific DNA binding transcription factors: setting the stage for a large-scale curation effort (2013, background): “This assembly can either be followed by immediate RNAP II-dependent transcription or it can result in promoter-proximal pausing of RNAP II that can subsequently be released into active transcription triggered by either DbTFs or other mechanisms (1, 6, 7).”