Causes and consequences of RNA polymerase II stalling during transcript elongation

González, Melvin Noé; Blears, Daniel; Svejstrup, Jesper Q.

doi:10.1038/s41580-020-00308-8

Cited by 158 publications

(121 citation statements)

References 231 publications

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“…Importantly, this first model considered that all RNAP molecules have the same properties and the same dynamics throughout the transcription unit. This, however, does not correspond to the reality of the transcription cycle, where RNAP frequently pauses and backtracks, notably in the termination zone (reviewed in Noe Gonzalez et al [2021]). We therefore built a second model (Fig 4D ), where RNAP may dynamically switch between an elongating, mobile form (in orange on Fig 4D ) and a backtracked, immobile state (in red on Fig 4D).…”

Section: Resultsmentioning

confidence: 99%

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes

et al. 2021

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The mechanisms leading to the accumulation of the SMC complexes condensins around specific transcription units remain unclear. Observations made in bacteria suggested that RNA polymerases (RNAPs) constitute an obstacle to SMC translocation, particularly when RNAP and SMC travel in opposite directions. Here we show in fission yeast that gene termini harbour intrinsic condensin-accumulating features whatever the orientation of transcription, which we attribute to the frequent backtracking of RNAP at gene ends. Consistent with this, to relocate backtracked RNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation of condensin at gene ends and to redistribute it evenly within transcription units, indicating that RNAP backtracking may play a key role in positioning condensin. Formalization of this hypothesis in a mathematical model suggests that the inclusion of a sub-population of RNAP with longer dwell-times is essential to fully recapitulate the distribution profiles of condensin around active genes. Taken together, our data strengthen the idea that dense arrays of proteins tightly bound to DNA alter the distribution of condensin on chromosomes.

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Section: Resultsmentioning

confidence: 99%

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes

et al. 2021

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“…To assess a biological readout of the repressive chromatin environment, we turned to phenotypic analysis of TFIIS disruption. TFIIS is a general elongation factor that rescues stalled Pol II; and nucleosomal barriers have been shown to increase stalled Pol II [45]. Given that Pol II stalling is common across the genome [46], it is paradoxical that the gene encoding TFIIS is not essential for viability in actively dividing cells, and its deletion does not cause strong growth defects [47].…”

Section: Resultsmentioning

confidence: 99%

RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry

Cucinotta

Dell

Braceros

et al. 2021

Preprint

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Quiescence is a reversible G0 state essential for differentiation, regeneration, stem cell renewal, and immune cell activation. Necessary for long-term survival, quiescent chromatin is compact, hypoacetylated, and transcriptionally inactive. How transcription activates upon cell-cycle re-entry is undefined. Here we report robust, widespread transcription within the first minutes of quiescence exit. During quiescence, the chromatin-remodeling enzyme RSC was already bound to the genes induced upon quiescence exit. RSC depletion caused severe quiescence exit defects: a global decrease in RNA polymerase II (Pol II) loading, Pol II accumulation at transcription start sites, initiation from ectopic upstream loci, and aberrant antisense transcription. These phenomena were due to a combination of highly robust Pol II transcription and severe chromatin defects in the promoter regions and gene bodies. Together, these results uncovered multiple mechanisms by which RSC facilitates initiation and maintenance of large-scale, rapid gene expression despite a globally repressive chromatin state.

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“…Additionally, analysis of RNA Polymerase II (RNAPII) dynamics upon deletion of the −5SE shows a complete loss of RNAPII at the Nanog promoter, indicating that the −5SE modulates Nanog expression by recruiting RNAPII or by promoting its conversion to its initiating form through phosphorylation of Ser 5 of the C-terminal domain (CTD, Figure 1C). Further analysis of the −45SE and its role in regulating Nanog gene expression is necessary to determine whether the two enhancers utilize the same or distinct mechanism(s) from the −5SE (Figure 1D; Henriques et al, 2018;Chen et al, 2018;Bartman et al, 2019;Sheridan et al, 2019;Zatreanu et al, 2019;Noe Gonzalez et al, 2020).…”

Section: Enhancersmentioning

confidence: 99%

Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions

Agrawal

Rao

2021

Front. Cell Dev. Biol.

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Cell fate decisions are the backbone of many developmental and disease processes. In early mammalian development, precise gene expression changes underly the rapid division of a single cell that leads to the embryo and are critically dependent on autonomous cell changes in gene expression. To understand how these lineage specifications events are mediated, scientists have had to look past protein coding genes to the cis regulatory elements (CREs), including enhancers and insulators, that modulate gene expression. One class of enhancers, termed super-enhancers, is highly active and cell-type specific, implying their critical role in modulating cell-type specific gene expression. Deletion or mutations within these CREs adversely affect gene expression and development and can cause disease. In this mini-review we discuss recent studies describing the potential roles of two CREs, enhancers and binding sites for CTCF, in early mammalian development.

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Causes and consequences of RNA polymerase II stalling during transcript elongation

Cited by 158 publications

References 231 publications

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes

RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry

Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions

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