Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome.

Autor:	Norppa AJ; Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Chowdhury I; Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland., van Rooijen LE; Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands., Ravantti JJ; Molecular and Integrative Biosciences Research Programme, University of Helsinki, Helsinki, Finland., Snel B; Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands., Varjosalo M; Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Frilander MJ; Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Apr 24; Vol. 52 (7), pp. 4037-4052.
DOI:	10.1093/nar/gkae070
Abstrakt:	Here, we identify RBM41 as a novel unique protein component of the minor spliceosome. RBM41 has no previously recognized cellular function but has been identified as a paralog of U11/U12-65K, a known unique component of the U11/U12 di-snRNP. Both proteins use their highly similar C-terminal RRMs to bind to 3'-terminal stem-loops in U12 and U6atac snRNAs with comparable affinity. Our BioID data indicate that the unique N-terminal domain of RBM41 is necessary for its association with complexes containing DHX8, an RNA helicase, which in the major spliceosome drives the release of mature mRNA from the spliceosome. Consistently, we show that RBM41 associates with excised U12-type intron lariats, is present in the U12 mono-snRNP, and is enriched in Cajal bodies, together suggesting that RBM41 functions in the post-splicing steps of the minor spliceosome assembly/disassembly cycle. This contrasts with U11/U12-65K, which uses its N-terminal region to interact with U11 snRNP during intron recognition. Finally, while RBM41 knockout cells are viable, they show alterations in U12-type 3' splice site usage. Together, our results highlight the role of the 3'-terminal stem-loop of U12 snRNA as a dynamic binding platform for the U11/U12-65K and RBM41 proteins, which function at distinct stages of the assembly/disassembly cycle. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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