Changes in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophy.

ABSTRACT: It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins (snRNPs): essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intranuclear snRNP mobility, we employed a panel of inhibitors of diffe

SUBMITTER: Clelland AK 

PROVIDER: S-EPMC3403233 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature