L. Pellizzoni et al., A NOVEL FUNCTION FOR SMN, THE SPINAL MUSCULAR-ATROPHY DISEASE GENE-PRODUCT, IN PRE-MESSENGER-RNA SPLICING, Cell (Cambridge), 95(5), 1998, pp. 615-624
Spinal muscular atrophy (SMA) is a common motor neuron degenerative di
sease that results from reduced levels of, or mutations in, the Surviv
al of Motor Neurons (SMN) protein. SMN is found in the cytoplasm and t
he nucleus where it is concentrated in gems. SMN interacts with splice
osomal snRNP proteins and is critical for snRNP assembly in the cytopl
asm. We show that a dominant-negative mutant SMN (SMN Delta N27) cause
s a dramatic reorganization of snRNPs in the nucleus. Furthermore, SMN
Delta N27 inhibits pre-mRNA splicing in vitro, while wild-type SMN st
imulates 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 bio
genesis, and they link the function of SMN in this pathway to SMA.