Molecular mechanisms in spinal muscular atrophy: models and perspectives

Curr Opin Neurol. 2001 Oct;14(5):629-34. doi: 10.1097/00019052-200110000-00012.

Abstract

Spinal muscular atrophy is an autosomal-recessive disorder that is caused by homozygous mutations or deletion of the telomeric copy of the survival of motor neurone (SMN) gene on human chromosome 5q13. The SMN gene is present as an inverted repeat in this chromosomal region, and both SMN genes are expressed. They differ by the preferential expression of a full-length transcript from the telomeric copy and a truncated SMN protein from the centromeric SMN gene, which lacks the carboxyl-terminal portions of the protein encoded by exon 7. The SMN protein is part of multiprotein complexes in the cytoplasm and the nucleus that are involved in spliceosomal small-nuclear RNP assembly. This function depends on interaction with spliceosomal Sm core proteins. Recent data have also shown that the SMN protein interacts with RNA polymerase II, thus implying additional functions in messenger RNA transcription, possibly by assembly of RNA polymerase II transcription complexes. Thus, the SMN protein is involved in critical steps of messenger RNA transcription and processing, and current research efforts are directed at identifying the specificity of these defects for the pathophysiological changes in motor neurones that occur in spinal muscular atrophy.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / physiopathology*