A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.

Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease that results from reduced levels of, or mutations in, the Survival of Motor Neurons (SMN) protein. SMN is found in the cytoplasm and the nucleus where it is concentrated in gems. SMN interacts with spliceosomal snRNP proteins and is critical for snRNP assembly in the cytoplasm. We show that a dominant-negative mutant SMN (SMNdeltaN27) causes a dramatic reorganization of snRNPs in the nucleus. Furthermore, SMNdeltaN27 inhibits pre-mRNA splicing in vitro, while wild-type SMN stimulates splicing. SMN mutants found in SMA patients cannot stimulate splicing. These findings demonstrate that SMN plays a crucial role in the generation of the pre-mRNA splicing machinery and thus in mRNA biogenesis, and they link the function of SMN in this pathway to SMA.

• Publication year

  1998

• Venue

  Cell

• Publication date

  1998-11-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S0092-8674(00)81632-3PMID 9845364
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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