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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Messenger-rna; Binding Proteins; Gene-expression; Motif; Relaxation; Target; Nmr
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2025
Prepublished im Jahr
0
HGF-Berichtsjahr
2025
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 53,
Heft: 15,
Seiten: ,
Artikelnummer: gkaf741
Supplement: ,
Reihe
Verlag
Oxford University Press
Verlagsort
Great Clarendon St, Oxford Ox2 6dp, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-503000-001
Förderungen
European Union NextGenerationEU
Next Generation EU
Marie Skłodowska-Curie Innovative Training Network (MSCA-ITN) RNAct
Copyright
Erfassungsdatum
2025-10-10