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Abstract
The survival of motor neurons (SMN) protein is essential for the biogenesis of small
nuclear RNA (snRNA)-ribonucleoproteins (snRNPs), the major components of the pre-mRNA
splicing machinery. Though it is ubiquitously expressed, SMN deficiency causes the
motor neuron degenerative disease spinal muscular atrophy (SMA). We show here that
SMN deficiency, similar to that which occurs in severe SMA, has unexpected cell type-specific
effects on the repertoire of snRNAs and mRNAs. It alters the stoichiometry of snRNAs
and causes widespread pre-mRNA splicing defects in numerous transcripts of diverse
genes, preferentially those containing a large number of introns, in SMN-deficient
mouse tissues. These findings reveal a key role for the SMN complex in RNA metabolism
and in splicing regulation and indicate that SMA is a general splicing disease that
is not restricted to motor neurons.