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
    
 
    
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        Schlagwörter
        Messenger-rna; Binding Proteins; Gene-expression; Motif; Relaxation; Target; Nmr
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2025
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2025
    
 
    
    
        ISSN (print) / ISBN
        0305-1048
    
 
    
        e-ISSN
        1362-4962
    
 
    
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	    Band: 53,  
	    Heft: 15,  
	    Seiten: ,  
	    Artikelnummer: gkaf741 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Oxford University Press
        
 
        
            Verlagsort
            Great Clarendon St, Oxford Ox2 6dp, England
        
 
	
        
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        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
    
 
    
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        Erfassungsdatum
        2025-10-10