[PDF][PDF] Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein

U Narayanan, T Achsel, R Lührmann, AG Matera - Molecular cell, 2004 - cell.com
U Narayanan, T Achsel, R Lührmann, AG Matera
Molecular cell, 2004cell.com
Cytoplasmic assembly of Sm-class small nuclear ribonucleoproteins (snRNPs) is a central
process in eukaryotic gene expression. A large macromolecular complex containing the
survival of motor neurons (SMN) protein is required for proper snRNP assembly in vivo.
Defects in SMN function lead to a human neuromuscular disorder, spinal muscular atrophy
(SMA). SMN protein localizes to both nuclear and cytoplasmic compartments, and a
reduction in nuclear levels of SMN is correlated with the disease. The mechanism of SMN …
Abstract
Cytoplasmic assembly of Sm-class small nuclear ribonucleoproteins (snRNPs) is a central process in eukaryotic gene expression. A large macromolecular complex containing the survival of motor neurons (SMN) protein is required for proper snRNP assembly in vivo. Defects in SMN function lead to a human neuromuscular disorder, spinal muscular atrophy (SMA). SMN protein localizes to both nuclear and cytoplasmic compartments, and a reduction in nuclear levels of SMN is correlated with the disease. The mechanism of SMN nuclear import, however, is unknown. Using digitonin-permeabilized cells, we show that SMN import depends on the presence of Sm snRNPs. Conversely, import of labeled U1 snRNPs was SMN complex dependent. Thus, import of SMN and U snRNPs are coupled in vitro. Furthermore, we identify nuclear import defects in SMA patient-derived SMN mutants, uncovering a potential mechanism for SMN dysfunction.
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