Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein

Citation
Md. Hebert et al., Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein, GENE DEV, 15(20), 2001, pp. 2720-2729
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
15
Issue
20
Year of publication
2001
Pages
2720 - 2729
Database
ISI
SICI code
0890-9369(20011015)15:20<2720:CFTBBC>2.0.ZU;2-F
Abstract
Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the human survival of motor neuron 1 gene, SMN1. SMN protein is part of a l arge complex that is required for biogenesis of various small nuclear ribon ucleoproteins (snRNPs). Here, we report that SMN interacts directly with th e Cajal body signature protein, coilin, and that this interaction mediates recruitment of the SMN complex to Cajal bodies. Mutation or deletion of spe cific RG dipeptide residues within coilin inhibits the interaction both in vivo and in vitro. Interestingly, GST-pulldown experiments show that coilin also binds directly to SmB'. Competition studies show that coilin competes with SmB' for binding sites on SMN. Ectopic expression of SMN and coilin c onstructs in mouse embryonic fibroblasts lacking endogenous coilin confirms that recruitment of SMN and splicing snRNPs to Cajal bodies depends on the coilin C-terminal RG motif. A cardinal feature of SMA patient cells is a d efect in the targeting of SMN to nuclear foci; our results uncover a role f or coilin in this process.