β-CASP proteins removing RNA polymerase from DNA: when a torpedo is needed to shoot a sitting duck

Wiedermannová, Jana; Krásný, Libor

doi:10.1093/nar/gkab803

Cited by 6 publications

(3 citation statements)

References 168 publications

(183 reference statements)

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“…Our study reveals that backtracking may actually have a positive impact, in that an active, reciprocating pathway with backtrackingrecovery cycles can promote efficient passage through relatively longlived roadblocks, which is critical to prevent RNAP from being stalled and targeted by exonucleolytic activity 34 . Our study also explains the different behavior of RNAP and helicase RecBCD when encountering the EcoRI roadblock.…”

Section: Discussionmentioning

confidence: 90%

Reciprocating RNA Polymerase batters through roadblocks

Qian,

Cartee,

et al. 2024

Nat Commun

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RNA polymerases must transit through protein roadblocks to produce full-length transcripts. Here we report real-time measurements of Escherichia coli RNA polymerase passing through different barriers. As intuitively expected, assisting forces facilitated, and opposing forces hindered, RNA polymerase passage through lac repressor protein bound to natural binding sites. Force-dependent differences were significant at magnitudes as low as 0.2 pN and were abolished in the presence of the transcript cleavage factor GreA, which rescues backtracked RNA polymerase. In stark contrast, opposing forces promoted passage when the rate of RNA polymerase backtracking was comparable to, or faster than the rate of dissociation of the roadblock, particularly in the presence of GreA. Our experiments and simulations indicate that RNA polymerase may transit after roadblocks dissociate, or undergo cycles of backtracking, recovery, and ramming into roadblocks to pass through. We propose that such reciprocating motion also enables RNA polymerase to break protein-DNA contacts that hold RNA polymerase back during promoter escape and RNA chain elongation. This may facilitate productive transcription in vivo.

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Section: Discussionmentioning

confidence: 90%

Reciprocating RNA Polymerase batters through roadblocks

Qian,

Cartee,

et al. 2024

Nat Commun

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“…This function of HelD is synergistically enhanced by δ, a small subunit of RNAP specific for Firmicutes (Juang and Helmann 1994 , Doherty et al 2010 , Motackova et al 2010 , Rabatinova et al 2013 , Kuban et al 2019 ), a phylum where B. subtilis belongs. HelD thus represents one of several mechanisms that ensure removal of RNAPs roadblocking DNA (Wiedermannova and Krasny 2021 ). This functional redundancy is probably reflected in the minor phenotypes of the absence of HelD—slower growth in the presence of elevated KCl concentration and prolonged lag phase after dilution of stationary phase cells into fresh medium (Wiedermannova et al 2014 ).…”

Section: Held—discovery and Functional Interaction With Rnapmentioning

confidence: 99%

What the Hel: recent advances in understanding rifampicin resistance in bacteria

Sudzinová

Šanderová

Kovaĺ

et al. 2022

FEMS Microbiology Reviews

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Rifampicin is a clinically important antibiotic that binds to, and blocks the DNA/RNA channel of bacterial RNA polymerase (RNAP). Stalled, nonfunctional RNAPs can be removed from DNA by HelD proteins; this is important for maintenance of genome integrity. Recently, it was reported that HelD proteins from high G + C Actinobacteria, called HelR, are able to dissociate rifampicin-stalled RNAPs from DNA and provide rifampicin resistance. This is achieved by the ability of HelR proteins to dissociate rifampicin from RNAP. The HelR-mediated mechanism of rifampicin resistance is discussed here, and the roles of HelD/HelR in the transcriptional cycle are outlined. Moreover, the possibility that the structurally similar HelD proteins from low G + C Firmicutes may be also involved in rifampicin resistance is explored. Finally, the discovery of the involvement of HelR in rifampicin resistance provides a blueprint for analogous studies to reveal novel mechanisms of bacterial antibiotic resistance.

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“…This is further facilitated by dephosphorylation of the elongation co-factor, SPT5, by the PNUTS-PP1 phosphatase (Cortazar et al 2019; Eaton et al 2020). Similar “torpedo” mechanisms are employed in lower eukaryotes, prokaryotes, and archaea (Sikova et al 2020; Wiedermannova and Krasny 2021). Some of these involve endonucleolytic cleavage and exoribonucleolytic activities (Sanders et al 2020).…”

Section: Introductionmentioning

confidence: 96%

DNA-directed termination of mammalian RNA polymerase II

Davidson,

Rouvière,

Sousa-Luís

et al. 2024

Preprint

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The best-studied mechanism of eukaryotic RNA polymerase II (RNAPII) transcriptional termination involves polyadenylation site-directed cleavage of the nascent RNA. The RNAPII-associated cleavage product is then degraded by XRN2, dislodging RNAPII from the DNA template. In contrast, prokaryotic RNAP and eukaryotic RNAPIII often terminate directly at T-tracts in the coding DNA strand. Here, we demonstrate a similar and omnipresent capability for mammalian RNAPII. XRN2- and T-tract-dependent termination are independent - the latter usually acting when XRN2 cannot be engaged. We show that T-tracts terminate snRNA transcription, previously thought to require the Integrator complex. Importantly, we find genome-wide termination at T-tracts in promoter-proximal regions, but not within protein-coding gene bodies. XRN2-dependent termination dominates downstream of protein-coding genes, but the T-tract process is sometimes employed. Overall, we demonstrate global DNA-directed attrition of RNAPII transcription, suggesting that RNAPs retain the potential to terminate over T-rich sequences throughout evolution.

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β-CASP proteins removing RNA polymerase from DNA: when a torpedo is needed to shoot a sitting duck

Cited by 6 publications

References 168 publications

Reciprocating RNA Polymerase batters through roadblocks

Reciprocating RNA Polymerase batters through roadblocks

What the Hel: recent advances in understanding rifampicin resistance in bacteria

DNA-directed termination of mammalian RNA polymerase II

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