A U1 snRNP-Specific Assembly Pathway Reveals the SMN Complex as a Versatile RNP Exchange
By B. So, L. Wan, Zhenxi Zhang, Pilong Li, Eric S. C. Babiash, Jingqi Duan, Ihab Younis, G. Dreyfuss. 2016
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Despite equal snRNP stoichiometry in spliceosomes, U1 snRNP (U1) is typically the most abundant vertebrate snRNP. Mechanisms regulating U1 overabundance and snRNP repertoire are unknown. In Sm-core assembly, a key snRNP-biogenesis step mediated by the SMN complex, the snRNA-specific RNA-binding protein (RBP) Gemin5 delivers pre-snRNAs, which join SMN–Gemin2–recruited Sm proteins. We show that the human U1-specific RBP U1-70K can bridge pre-U1 to SMN–Gemin2–Sm, in a Gemin5-independent manner, thus establishing an additional and U1-exclusive Sm core–assembly pathway. U1-70K hijacks SMN–Gemin2–Sm, enhancing Sm-core assembly on U1s and inhibiting that on other snRNAs, thereby promoting U1 overabundance and regulating snRNP repertoire. SMN–Gemin2's ability to facilitate transactions between different RBPs and RNAs explains its multi-RBP valency and the myriad transcriptome perturbations associated with SMN deficiency in neurodegenerative spinal muscular atrophy. We propose that SMN–Gemin2 is a versatile hub for RNP exchange that functions broadly in RNA metabolism.
Subfields: Genetics, Molecular Biology
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Citations in the corpus
- Iterative random forests to discover predictive and stable high-order interactions (2017, background): “The activity of the spliceosome, the ribonucleoprotein responsible for most splicing in eukaryotic genomes, is driven by complex, cell-type–specific interactions with cohorts of RNA-binding proteins (RBP) (39, 40), suggesting that high-order interactions play an important role in the regulation of al”