Mechanisms of transcription attenuation and condensation of RNA polymerase II by RECQ5 helicase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00138837" target="_blank" >RIV/00216224:14740/24:00138837 - isvavai.cz</a>

Výsledek na webu

<a href="https://www2.rnasociety.org/conferences/rna-2024/meeting-information/" target="_blank" >https://www2.rnasociety.org/conferences/rna-2024/meeting-information/</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Mechanisms of transcription attenuation and condensation of RNA polymerase II by RECQ5 helicase

Popis výsledku v původním jazyce

The elongation rates of RNA polymerase II (RNAPII) require precise control to prevent transcriptional stress, which can impede co‐transcriptional pre‐mRNA processing and contribute to many age‐ or disease‐associated molecular changes (e.g., loss of proteostasis). Additionally, mesoscale organization of transcription is thought to control the transcriptional rates and multiple factors have been reported to form biomolecular condensates and integrate RNAPII through the interaction with the C‐terminal domain (CTD) of the largest subunit, RPB1. However, the structural organization of these condensates remains uncharacterized due to their small size and inherently dynamic nature. Here, we investigated the molecular mechanisms by which a general transcription factor – RECQ5 – associates with hyperphosphorylated RNAPII elongation complex (P‐RNAPII EC) and controls translocation of RNAPII along genes. We combined biochemical reconstitution, electron cryomicroscopy, cryotomography, and coarse‐grained simulations. We report two mechanisms by which RECQ5 modulates RNAPII transcription. At the atomic level, we demonstrate that RECQ5 uses the brake‐helix as a doorstop to control RNAPII translocation along DNA, attenuating transcription. At the mesoscale level, RECQ5 forms a condensate scaffold matrix, integrating P‐RNAPII EC through a network of site‐specific interactions, reinforcing the condensate’s structural integrity. Our integrative, multi‐scale study provides insights into the structural basis of transcription attenuation and into the molecular architecture and biogenesis of a model RNAPII condensate.

Název v anglickém jazyce

Mechanisms of transcription attenuation and condensation of RNA polymerase II by RECQ5 helicase

Popis výsledku anglicky

The elongation rates of RNA polymerase II (RNAPII) require precise control to prevent transcriptional stress, which can impede co‐transcriptional pre‐mRNA processing and contribute to many age‐ or disease‐associated molecular changes (e.g., loss of proteostasis). Additionally, mesoscale organization of transcription is thought to control the transcriptional rates and multiple factors have been reported to form biomolecular condensates and integrate RNAPII through the interaction with the C‐terminal domain (CTD) of the largest subunit, RPB1. However, the structural organization of these condensates remains uncharacterized due to their small size and inherently dynamic nature. Here, we investigated the molecular mechanisms by which a general transcription factor – RECQ5 – associates with hyperphosphorylated RNAPII elongation complex (P‐RNAPII EC) and controls translocation of RNAPII along genes. We combined biochemical reconstitution, electron cryomicroscopy, cryotomography, and coarse‐grained simulations. We report two mechanisms by which RECQ5 modulates RNAPII transcription. At the atomic level, we demonstrate that RECQ5 uses the brake‐helix as a doorstop to control RNAPII translocation along DNA, attenuating transcription. At the mesoscale level, RECQ5 forms a condensate scaffold matrix, integrating P‐RNAPII EC through a network of site‐specific interactions, reinforcing the condensate’s structural integrity. Our integrative, multi‐scale study provides insights into the structural basis of transcription attenuation and into the molecular architecture and biogenesis of a model RNAPII condensate.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EH22_008%2F0004575" target="_blank" >EH22_008/0004575: RNA pro terapii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů