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Pérez-Ràfols, A.* ; Pérez-Ropero, G.* ; Cerofolini, L.* ; Sperotto, L. ; Roca-Martínez, J.* ; Higuera-Rodriguez, R.A.* ; Russomanno, P.* ; Kaiser, W.J.* ; Vranken, W.F.* ; Danielson, U.H.* ; Provenzani, A.* ; Martelli, T.* ; Sattler, M. ; Buijs, J.* ; Fragai, M.*

Deciphering the RNA recognition by Musashi-1 to design protein and RNA variants for in vitro and in vivo applications.

Nucleic Acids Res. 53:gkaf741 (2025)
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The Human Musashi-1 (MSI-1) is an RNA-binding protein that recognizes (G/A)U1-3AGU and UAG sequences in diverse RNAs through two RNA Recognition Motif (RRM) domains and regulates the fate of target RNA. Here, we have combined structural biology and computational approaches to analyse the binding of the RRM domains of human MSI-1 with single-stranded and structured RNA ligands. We have used our recently developed computational tool RRMScorer to design a set of substitutions in the MSI-1 protein and the investigated RNA strands to modulate the binding affinity and selectivity. The in silico predictions of the designed protein-RNA interactions are assessed by nuclear magnetic resonance and surface plasmon resonance. These experiments have also been used to study the competition of the two RRM domains of MSI-1 for the same binding site within linear and harpin RNA. Our experimental results shed light on MSI-RNA interactions, thus opening the way for the development of new biomolecules for in vitro and in vivo studies and downstream applications.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Messenger-rna; Binding Proteins; Gene-expression; Motif; Relaxation; Target; Nmr
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Volume: 53, Issue: 15, Pages: , Article Number: gkaf741 Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503000-001
Grants European Union NextGenerationEU
Next Generation EU
Marie Skłodowska-Curie Innovative Training Network (MSCA-ITN) RNAct
Scopus ID 105013116448
PubMed ID 40795964
Erfassungsdatum 2025-10-10