Mfd Dynamically Regulates Transcription via a Release and Catch-Up Mechanism

Le, Tung T.; Yang, Yi; Tan, Chuang; Suhanovsky, Margaret M.; Fulbright, Robert M.; Inman, James T.; Li, Ming; Lee, Jaeyoon; Perelman, Sarah; Roberts, Jeffrey W.; Deaconescu, Alexandra M.; Wang, Michelle D.

doi:10.1016/j.cell.2018.06.002

Cited by 35 publications

(87 citation statements)

References 1 publication

(1 reference statement)

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“…It was recently proposed that the Mfd translocase in Escherichia coli could both nudge forward weakly paused RNAP and induce the dissociation of stalled RNAP using a release and catch-up mechanism (Le et al, 2018). It was recently proposed that the Mfd translocase in Escherichia coli could both nudge forward weakly paused RNAP and induce the dissociation of stalled RNAP using a release and catch-up mechanism (Le et al, 2018).…”

Section: Lack Of Sen1 Impacts Rnap3 Trna Levelsmentioning

confidence: 99%

Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription

et al. 2019

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R‐loop disassembly by the human helicase Senataxin contributes to genome integrity and to proper transcription termination at a subset of RNA polymerase II genes. Whether Senataxin also contributes to transcription termination at other classes of genes has remained unclear. Here, we show that Sen1, one of two fission yeast homologues of Senataxin, promotes efficient termination of RNA polymerase III (RNAP3) transcription in vivo. In the absence of Sen1, RNAP3 accumulates downstream of RNAP3‐transcribed genes and produces long exosome‐sensitive 3′‐extended transcripts. Importantly, neither of these defects was affected by the removal of R‐loops. The finding that Sen1 acts as an ancillary factor for RNAP3 transcription termination in vivo challenges the pre‐existing view that RNAP3 terminates transcription autonomously. We propose that Sen1 is a cofactor for transcription termination that has been co‐opted by different RNA polymerases in the course of evolution.

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Section: Lack Of Sen1 Impacts Rnap3 Trna Levelsmentioning

confidence: 99%

Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription

et al. 2019

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“…These factors are ATP-dependent (Epshtein et al, 2010;Le et al, 2018). These factors are ATP-dependent (Epshtein et al, 2010;Le et al, 2018).…”

Section: Rnase J1 and Its Role In Disassembly Of Transcription Complexesmentioning

confidence: 99%

“…These stalled complexes can be resolved by various factors that either allow RNAP to proceed with transcription or liberate RNAP from the stalled complex (Toulme et al, 2000;Peters et al, 2009;Epshtein et al, 2014;Fan et al, 2016). These factors include (i) the termination factor Rho (Epshtein et al, 2010), (ii) the transcription-repair coupling factor, Mfd, that recognizes stalled RNAPs and which recruits UvrA to initiate nucleotide excision repair (Le et al, 2018), and (iii) GreA, a translation elongation factor that induces hydrolysis of RNA by RNAP in backtracked complexes (Kusuya et al, 2011). These factors are vital for physiologically appropriate gene expression as well as for genome integrity (Nadkarni et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The torpedo effect inBacillus subtilis:RNase J1 resolves stalled transcription complexes

et al. 2019

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RNase J1 is the major 5 0 -to-3 0 bacterial exoribonuclease. We demonstrate that in its absence, RNA polymerases (RNAPs) are redistributed on DNA, with increased RNAP occupancy on some genes without a parallel increase in transcriptional output. This suggests that some of these RNAPs represent stalled, non-transcribing complexes. We show that RNase J1 is able to resolve these stalled RNAP complexes by a "torpedo" mechanism, whereby RNase J1 degrades the nascent RNA and causes the transcription complex to disassemble upon collision with RNAP. A heterologous enzyme, yeast Xrn1 (5 0 -to-3 0 exonuclease), is less efficient than RNase J1 in resolving stalled Bacillus subtilis RNAP, suggesting that the effect is RNase-specific. Our results thus reveal a novel general principle, whereby an RNase can participate in genome-wide surveillance of stalled RNAP complexes, preventing potentially deleterious transcription-replication collisions.

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“…We next tested roadblock‐enhanced occlusion in a synthetic construct with convergent promoters in which Lac repressor was used to stall RNAP such that it overlapped one of the promoters and thereby interfered with its transcription. We saw strong roadblock‐enhanced TI in an E. coli mfd mutant, in which termination of stalled RNAPs is defective , including at protein roadblocks . However, the TI enhancement in mfd wild‐type cells was modest, with modelling indicating that roadblock‐enhanced occlusion is limited by rapid removal of RNAPs by Mfd unless the interfering promoter is strong.…”

mentioning

confidence: 86%

RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

et al. 2019

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Convergent promoters exert transcriptional interference ( TI ) by several mechanisms including promoter occlusion, where elongating RNA polymerases ( RNAP s) block access to a promoter. Here, we tested whether pausing of RNAP s by obstructive DNA ‐bound proteins can enhance TI by promoter occlusion. Using the Lac repressor as a ‘roadblock’ to induce pausing over a target promoter, we found only a small increase in TI , with mathematical modelling suggesting that rapid termination of the stalled RNAP was limiting the occlusion effect. As predicted, the roadblock‐enhanced occlusion was significantly increased in the absence of the Mfd terminator protein. Thus, protein roadblocking of RNAP may cause pause‐enhanced occlusion throughout genomes, and the removal of stalled RNAP may be needed to minimize unwanted TI .

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Mfd Dynamically Regulates Transcription via a Release and Catch-Up Mechanism

Cited by 35 publications

References 1 publication

Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription

Senataxin homologue Sen1 is required for efficient termination of RNA polymerase III transcription

The torpedo effect inBacillus subtilis:RNase J1 resolves stalled transcription complexes

RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

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