Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death
AUTOR(ES)
Jablonka, Sibylle
FONTE
The National Academy of Sciences
RESUMO
Neuronal degeneration in spinal muscular atrophy is caused by reduced expression of the survival motor neuron (SMN) protein. SMN and the tightly interacting Gemin2 form part of a macromolecular complex (SMN complex) that mediates assembly of spliceosomal small nuclear ribonucleoproteins (U snRNPs). We used mouse genetics to investigate the function of this complex in motoneuron maintenance. Reduced Smn/Gemin2 protein levels lead to disturbed U snRNP assembly as indicated by reduced nuclear accumulation of Sm proteins. This finding correlates with enhanced motoneuron degeneration in Gemin2+/−/Smn+/− mice. Our data provide in vivo evidence that impaired production of U snRNPs contributes to motoneuron degeneration.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=126635Documentos Relacionados
- In vitro reconstitution of mammalian U2 and U5 snRNPs active in splicing: Sm proteins are functionally interchangeable and are essential for the formation of functional U2 and U5 snRNPs.
- U3, U8 and U13 comprise a new class of mammalian snRNPs localized in the cell nucleolus.
- In vitro assembly of U1 snRNPs.
- U1-U2 snRNPs interaction induced by an RNA complementary to the 5' end sequence of U1 snRNA.
- A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice