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

Abstract

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.

• Authors: L Pellizzoni, N Kataoka, B Charroux, G Dreyfuss
• Journal: Cell (Cell) Vol. 95 Issue 5 Pg. 615-24 (Nov 25 1998) ISSN: 0092-8674 [Print] United States
• PMID: 9845364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantigens
• Cyclic AMP Response Element-Binding Protein
• Nerve Tissue Proteins
• Nuclear Proteins
• Phosphoproteins
• RNA Precursors
• RNA-Binding Proteins
• Ribonucleoproteins, Small Nuclear
• SMN Complex Proteins
• p80-coilin

Topics

• Autoantigens (metabolism)
• Cyclic AMP Response Element-Binding Protein
• HeLa Cells
• Humans
• Microscopy, Fluorescence
• Muscular Atrophy, Spinal (genetics)
• Nerve Tissue Proteins (genetics, physiology)
• Nuclear Proteins (metabolism)
• Open Reading Frames
• Organelles (metabolism, ultrastructure)
• Phosphoproteins (metabolism)
• RNA Precursors (genetics)
• RNA Splicing
• RNA-Binding Proteins
• Ribonucleoproteins, Small Nuclear (metabolism)
• SMN Complex Proteins
• Spliceosomes (metabolism)