A U1 snRNP-specific assembly pathway reveals the SMN complex as a versatile hub for RNP exchange

Nat Struct Mol Biol. 2016 Mar;23(3):225-30. doi: 10.1038/nsmb.3167. Epub 2016 Feb 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Metabolic Networks and Pathways*
  • Models, Molecular
  • Nerve Tissue Proteins / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoprotein, U1 Small Nuclear / chemistry
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*
  • SMN Complex Proteins / metabolism

Substances

  • GEMIN2 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • SMN Complex Proteins