Implication of the SMN complex in the biogenesis and steady state level of the signal recognition particle.
Détails
ID Serval
serval:BIB_01FF74FD2A0D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Implication of the SMN complex in the biogenesis and steady state level of the signal recognition particle.
Périodique
Nucleic acids research
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Statut éditorial
Publié
Date de publication
01/2013
Peer-reviewed
Oui
Volume
41
Numéro
2
Pages
1255-1272
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Spinal muscular atrophy is a severe motor neuron disease caused by reduced levels of the ubiquitous Survival of MotoNeurons (SMN) protein. SMN is part of a complex that is essential for spliceosomal UsnRNP biogenesis. Signal recognition particle (SRP) is a ribonucleoprotein particle crucial for co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum. SRP biogenesis is a nucleo-cytoplasmic multistep process in which the protein components, except SRP54, assemble with 7S RNA in the nucleolus. Then, SRP54 is incorporated after export of the pre-particle into the cytoplasm. The assembly factors necessary for SRP biogenesis remain to be identified. Here, we show that 7S RNA binds to purified SMN complexes in vitro and that SMN complexes associate with SRP in cellular extracts. We identified the RNA determinants required. Moreover, we report a specific reduction of 7S RNA levels in the spinal cord of SMN-deficient mice, and in a Schizosaccharomyces pombe strain carrying a temperature-degron allele of SMN. Additionally, microinjected antibodies directed against SMN or Gemin2 interfere with the association of SRP54 with 7S RNA in Xenopus laevis oocytes. Our data show that reduced levels of the SMN protein lead to defect in SRP steady-state level and describe the SMN complex as the first identified cellular factor required for SRP biogenesis.
Mots-clé
Alleles, Animals, Antibodies/pharmacology, Base Sequence, Cytoplasm/metabolism, HeLa Cells, Humans, Mice, Molecular Sequence Data, Muscular Atrophy, Spinal/metabolism, Mutation, RNA, Small Cytoplasmic/chemistry, RNA, Small Cytoplasmic/metabolism, RNA, Small Nuclear/metabolism, SMN Complex Proteins/antagonists & inhibitors, SMN Complex Proteins/immunology, SMN Complex Proteins/metabolism, Schizosaccharomyces/genetics, Signal Recognition Particle/chemistry, Signal Recognition Particle/metabolism, Spinal Cord/metabolism, Xenopus laevis
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/03/2014 10:02
Dernière modification de la notice
23/02/2024 13:45