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Transient pausing by RNA polymerase II

Authors: David H. Price;

Transient pausing by RNA polymerase II

Abstract

RNA polymerase II (Pol II) elongation control is utilized during transcription of most metazoan genes (1). Polymerases that successfully initiate must first break contacts with initiation factors and then interact with elongation factors including the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF). This leads to a reduction of the elongation rate due to an increase in pausing. The stage is now set for positive transcription elongation factor b (P-TEFb) to phosphorylate DSIF, which, in turn, leads to the loss of NELF, association of the PAF1 complex, and the onset of productive elongation. Although it is clear that paused Pol II is found in promoter-proximal regions of most expressed genes in metazoan cells, a controversy has arisen concerning how long paused polymerases remain engaged. The prevailing view is that paused Pol II is relatively stable. However, the findings presented in PNAS by Steurer et al. (2) call this view into question. They generated a human cell line solely expressing GFP-tagged Pol II and then used fluorescence recovery after photobleaching (FRAP) to identify and characterize four distinguishable kinetic states for Pol II. Besides the very rapid recovery due to diffusion of free Pol II, they found three bound states, each with about an order of magnitude slower recovery than the preceding one. These kinetic states were assigned to initiation, pausing, and productive elongation by observing how well-characterized compounds affected the FRAP measurements. Steurer et al. (2) used computational modeling of the FRAP data to calculate the residence time for Pol II in each of the three bound states, as well as the fraction of each state that progresses into the next state (Fig. 1). They found that in normal untreated cells, Pol II spends, on average, 2.4 s interacting with the promoter. About 90% of these polymerases dissociate because … [↵][1]1Email: david-price{at}uiowa.edu. [1]: #xref-corresp-1-1

Related Organizations
Keywords

Transcription, Genetic, DNA-Directed RNA Polymerases, RNA Polymerase II, Promoter Regions, Genetic

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
36
Top 10%
Average
Top 10%
bronze