Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein

Mol Cell. 2004 Oct 22;16(2):223-34. doi: 10.1016/j.molcel.2004.09.024.

Abstract

Cytoplasmic assembly of Sm-class small nuclear ribonucleoproteins (snRNPs) is a central process in eukaryotic gene expression. A large macromolecular complex containing the survival of motor neurons (SMN) protein is required for proper snRNP assembly in vivo. Defects in SMN function lead to a human neuromuscular disorder, spinal muscular atrophy (SMA). SMN protein localizes to both nuclear and cytoplasmic compartments, and a reduction in nuclear levels of SMN is correlated with the disease. The mechanism of SMN nuclear import, however, is unknown. Using digitonin-permeabilized cells, we show that SMN import depends on the presence of Sm snRNPs. Conversely, import of labeled U1 snRNPs was SMN complex dependent. Thus, import of SMN and U snRNPs are coupled in vitro. Furthermore, we identify nuclear import defects in SMA patient-derived SMN mutants, uncovering a potential mechanism for SMN dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / metabolism
  • Cyclic AMP Response Element-Binding Protein
  • HeLa Cells
  • Humans
  • Membrane Transport Proteins
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • RNA / metabolism
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • SMN Complex Proteins
  • beta Karyopherins / metabolism

Substances

  • Carrier Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • SMN Complex Proteins
  • ZPR1 protein, human
  • beta Karyopherins
  • RNA