YB-1 unwinds mRNA secondary structures in vitro and negatively regulates stress granule assembly in HeLa cells.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
27 09 2021
Historique:
accepted: 16 08 2021
revised: 12 08 2021
received: 25 06 2021
pubmed: 2 9 2021
medline: 21 12 2021
entrez: 1 9 2021
Statut: ppublish

Résumé

In the absence of the scanning ribosomes that unwind mRNA coding sequences and 5'UTRs, mRNAs are likely to form secondary structures and intermolecular bridges. Intermolecular base pairing of non polysomal mRNAs is involved in stress granule (SG) assembly when the pool of mRNAs freed from ribosomes increases during cellular stress. Here, we unravel the structural mechanisms by which a major partner of dormant mRNAs, YB-1 (YBX1), unwinds mRNA secondary structures without ATP consumption by using its conserved cold-shock domain to destabilize RNA stem/loops and its unstructured C-terminal domain to secure RNA unwinding. At endogenous levels, YB-1 facilitates SG disassembly during arsenite stress recovery. In addition, overexpression of wild-type YB-1 and to a lesser extent unwinding-defective mutants inhibit SG assembly in HeLa cells. Through its mRNA-unwinding activity, YB-1 may thus inhibit SG assembly in cancer cells and package dormant mRNA in an unfolded state, thus preparing mRNAs for translation initiation.

Identifiants

pubmed: 34469566
pii: 6362110
doi: 10.1093/nar/gkab748
pmc: PMC8464072
doi:

Substances chimiques

Arsenites 0
RNA, Messenger 0
Y-Box-Binding Protein 1 0
YBX1 protein, human 0
Adenosine Triphosphate 8L70Q75FXE
arsenite N5509X556J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10061-10081

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Karina Budkina (K)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.
Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation.

Krystel El Hage (K)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Marie-Jeanne Clément (MJ)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Bénédicte Desforges (B)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Ahmed Bouhss (A)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Vandana Joshi (V)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Alexandre Maucuer (A)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Loic Hamon (L)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

Lev P Ovchinnikov (LP)

Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation.

Dmitry N Lyabin (DN)

Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation.

David Pastré (D)

SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.

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