mRNA and DNA selection via protein multimerization: YB-1 as a case study.
Translation is tightly regulated in cells for keeping adequate protein levels, this task being notably accomplished by dedicated mRNA-binding proteins recognizing a specific set of mRNAs to repress or facilitate their translation. To select specific mRNAs, mRNA-binding proteins can strongly bind to specific mRNA sequences/structures. However, many mRNA-binding proteins rather display a weak specificity to short and redundant sequences. Here we examined an alternative mechanism by which mRNA-binding proteins could inhibit the translation of specific mRNAs, using YB-1, a major translation regulator, as a case study. Based on a cooperative binding, YB-1 forms stable homo-multimers on some mRNAs while avoiding other mRNAs. Via such inhomogeneous distribution, YB-1 can selectively inhibit translation of mRNAs on which it has formed stable multimers. This novel mechanistic view on mRNA selection may be shared by other proteins considering the elevated occurrence of multimerization among mRNA-binding proteins. Interestingly, we also demonstrate how, by using the same mechanism, YB-1 can form multimers on specific DNA structures, which could provide novel insights into YB-1 nuclear functions in DNA repair and multi-drug resistance.
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Dmitry A
DA
Kretov
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France.
Patrick A
PA
Curmi
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France.
Loic
L
Hamon
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France.
Sanae
S
Abrakhi
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France.
Bénédicte
B
Desforges
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Lev P
LP
Ovchinnikov
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204 and Université Evry-Val d'Essonne, Evry, 91025 France david.pastre@univ-evry.fr.
David
D
Pastré
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism* / Q000648:ultrastructure; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D014176:Protein Biosynthesis; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D004278:DNA, Superhelical; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; D004247:DNA; D004250:DNA Topoisomerases, Type II