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

doi:10.1016/j.molcel.2023.05.028

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^*

^*Corresponding author af dette arbejde

Institut for Molekylærbiologi og Genetik - RNA-biologi og -innovation

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

20 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Molecular Cell
Vol/bind	83
Nummer	13
Sider (fra-til)	2240-2257
Antal sider	18
ISSN	1097-2765
DOI	https://doi.org/10.1016/j.molcel.2023.05.028
Status	Udgivet - jul. 2023

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Rouvière, J. O., Salerno-Kochan, A., Lykke-Andersen, S., Garland, W., Dou, Y., Rathore, O., Molska, E. Š., Wu, G., Schmid, M., Bugai, A., Jakobsen, L., Žumer, K., Cramer, P., Andersen, J. S., Conti, E., & Jensen, T. H. (2023). ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts. Molecular Cell, 83(13), 2240-2257. https://doi.org/10.1016/j.molcel.2023.05.028

@article{868ab5346b7c444c93c7ca2b92c84c4d,

title = "ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts",

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.",

keywords = "ARS2, CPA complex, early transcription termination, INT complex, NEXT, PAXT, RNA decay, ZC3H4",

author = "Rouvi{\`e}re, {J{\'e}r{\^o}me O.} and Anna Salerno-Kochan and S{\o}ren Lykke-Andersen and William Garland and Yuhui Dou and Om Rathore and Molska, {Ewa {\v S}midov{\'a}} and Guifen Wu and Manfred Schmid and Andrii Bugai and Lis Jakobsen and Kristina {\v Z}umer and Patrick Cramer and Andersen, {Jens S.} and Elena Conti and Jensen, {Torben Heick}",

year = "2023",

month = jul,

doi = "10.1016/j.molcel.2023.05.028",

language = "English",

volume = "83",

pages = "2240--2257",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "13",

}

Rouvière, JO, Salerno-Kochan, A, Lykke-Andersen, S , Garland, W , Dou, Y, Rathore, O, Molska, EŠ, Wu, G, Schmid, M, Bugai, A, Jakobsen, L, Žumer, K, Cramer, P, Andersen, JS, Conti, E & Jensen, TH 2023, 'ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts', Molecular Cell, bind 83, nr. 13, s. 2240-2257. https://doi.org/10.1016/j.molcel.2023.05.028

ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts. / Rouvière, Jérôme O.; Salerno-Kochan, Anna; Lykke-Andersen, Søren et al.
I: Molecular Cell, Bind 83, Nr. 13, 07.2023, s. 2240-2257.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts

AU - Rouvière, Jérôme O.

AU - Salerno-Kochan, Anna

AU - Lykke-Andersen, Søren

AU - Garland, William

AU - Dou, Yuhui

AU - Rathore, Om

AU - Molska, Ewa Šmidová

AU - Wu, Guifen

AU - Schmid, Manfred

AU - Bugai, Andrii

AU - Jakobsen, Lis

AU - Žumer, Kristina

AU - Cramer, Patrick

AU - Andersen, Jens S.

AU - Conti, Elena

AU - Jensen, Torben Heick

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - ARS2

KW - CPA complex

KW - early transcription termination

KW - INT complex

KW - NEXT

KW - PAXT

KW - RNA decay

KW - ZC3H4

UR - http://www.scopus.com/inward/record.url?scp=85164271697&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2023.05.028

DO - 10.1016/j.molcel.2023.05.028

M3 - Journal article

C2 - 37329882

AN - SCOPUS:85164271697

SN - 1097-2765

VL - 83

SP - 2240

EP - 2257

JO - Molecular Cell

JF - Molecular Cell

IS - 13

ER -

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

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