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

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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.

Original languageEnglish
JournalMolecular Cell
Pages (from-to)2240-2257
Number of pages18
Publication statusPublished - Jul 2023

Bibliographical note

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Copyright © 2023 Elsevier Inc. All rights reserved.

    Research areas

  • ARS2, CPA complex, early transcription termination, INT complex, NEXT, PAXT, RNA decay, ZC3H4

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