ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts

Jérôme O. Rouvière, Anna Salerno-Kochan, Søren Lykke-Andersen, William Garland, Yuhui Dou, Om Rathore, Ewa Šmidová Molska, Guifen Wu, Manfred Schmid, Andrii Bugai, Lis Jakobsen, Kristina Žumer, Patrick Cramer, Jens S. Andersen, Elena Conti, Torben Heick Jensen*

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Abstract

The RNA-binding ARS2 protein is centrally involved in both early RNA polymerase II (RNAPII) transcription termination and transcript decay. Despite its essential nature, the mechanisms by which ARS2 enacts these functions have remained unclear. Here, we show that a conserved basic domain of ARS2 binds a corresponding acidic-rich, short linear motif (SLiM) in the transcription restriction factor ZC3H4. This interaction recruits ZC3H4 to chromatin to elicit RNAPII termination, independent of other early termination pathways defined by the cleavage and polyadenylation (CPA) and Integrator (INT) complexes. We find that ZC3H4, in turn, forms a direct connection to the nuclear exosome targeting (NEXT) complex, hereby facilitating rapid degradation of the nascent RNA. Hence, ARS2 instructs the coupled transcription termination and degradation of the transcript onto which it is bound. This contrasts with ARS2 function at CPA-instructed termination sites where the protein exclusively partakes in RNA suppression via post-transcriptional decay.

OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind83
Udgave nummer13
Sider (fra-til)2240-2257
ISSN1097-2765
DOI
StatusUdgivet - 6. jul. 2023

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Copyright © 2023 Elsevier Inc. All rights reserved.

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