RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 11 2023
Historique:
received: 31 08 2022
accepted: 27 10 2023
medline: 9 11 2023
pubmed: 8 11 2023
entrez: 7 11 2023
Statut: epublish

Résumé

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the B

Identifiants

pubmed: 37935663
doi: 10.1038/s41467-023-42962-4
pii: 10.1038/s41467-023-42962-4
pmc: PMC10630445
doi:

Substances chimiques

Ribonucleoprotein, U2 Small Nuclear 0
RNA 63231-63-0
RNA, Small Nuclear 0
U2 small nuclear RNA 0
NPL3 protein, S cerevisiae 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

7166

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ahmed Moursy (A)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland.
Novartis Institutes for BioMedical Research, Basel, Switzerland.

Antoine Cléry (A)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland. antoine.clery@bc.biol.ethz.ch.

Stefan Gerhardy (S)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland.
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Sardona Therapeutics, San Francisco, CA, USA.

Katharina M Betz (KM)

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Sanjana Rao (S)

Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.

Jarosław Mazur (J)

Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.

Sébastien Campagne (S)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland.
ARNA laboratory, INSERM U1212, University of Bordeaux, Bordeaux, France.

Irene Beusch (I)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

Malgorzata M Duszczyk (MM)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland.

Mark D Robinson (MD)

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Vikram Govind Panse (VG)

Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland. vpanse@imm.uzh.ch.
Faculty of Science, University of Zurich, Zurich, Switzerland. vpanse@imm.uzh.ch.

Frédéric H-T Allain (FH)

Department of Biology, Institute of Biochemistry, ETH Zurich, Switzerland. allain@bc.biol.ethz.ch.

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