Interaction between the small-nuclear-RNA cap hypermethylase and the spinal muscular atrophy protein, survival of motor neuron

EMBO Rep. 2003 Jun;4(6):616-22. doi: 10.1038/sj.embor.embor863.

Abstract

The biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) requires the cytoplasmic assembly of the Sm-core complex, followed by the hypermethylation of the small nuclear RNA (snRNA) 5' cap. Both the Sm-core complex and the snRNA trimethylguanosine cap are required for the efficient nuclear import of snRNPs. Here, we show that trimethylguanosine synthase 1 (TGS1), the human homologue of the yeast snRNA cap hypermethylase, interacts directly with the survival of motor neuron (SMN) protein. Both proteins are similarly distributed, localizing in the cytoplasm and in nuclear Cajal bodies. The interaction between TGS1 and SMN is disrupted by a mutation in SMN that mimics the predominant isoform of the protein that is expressed in patients with the neurodegenerative disease, spinal muscular atrophy. These data indicate that, in addition to its function in cytoplasmic Sm-core assembly, the SMN protein also functions in the recruitment of the snRNA cap hypermethylase.

Publication types

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

MeSH terms

  • Autoantigens
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • Models, Biological
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms
  • RNA Cap-Binding Proteins
  • RNA, Small Nuclear / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Ribonucleoproteins, Small Nuclear / chemistry*
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Tissue Distribution
  • snRNP Core Proteins

Substances

  • Autoantigens
  • Protein Isoforms
  • RNA Cap-Binding Proteins
  • RNA, Small Nuclear
  • Receptors, Cytoplasmic and Nuclear
  • Ribonucleoproteins, Small Nuclear
  • SNRPN protein, human
  • SNUPN protein, human
  • snRNP Core Proteins
  • Methyltransferases
  • trimethylguanosine synthase
  • Glutathione Transferase