title: Implication of the SMN complex in the biogenesis and steady state level of the signal recognition particle.
abstract: 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.
authors.affiliation: Laboratoire ARN-RNP structure-fonction-maturation, Enzymologie Moléculaire et Structurale (AREMS), Nancy Université-CNRS, UMR 7214, FR 3209, Faculté de Médecine de Nancy, BP 184, 9 avenue de la forêt de Haye, 54506 Vandoeuvre-les-Nancy Cedex, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Piazzon
authors.forename: Florence
authors.initials: F
authors.lastname: Schlotter
authors.forename: Suzie
authors.initials: S
authors.lastname: Lefebvre
authors.forename: Maxime
authors.initials: M
authors.lastname: Dodré
authors.forename: Agnès
authors.initials: A
authors.lastname: Méreau
authors.forename: Johann
authors.initials: J
authors.lastname: Soret
authors.forename: Aurore
authors.initials: A
authors.lastname: Besse
authors.forename: Martine
authors.initials: M
authors.lastname: Barkats
authors.forename: Rémy
authors.initials: R
authors.lastname: Bordonné
authors.forename: Christiane
authors.initials: C
authors.lastname: Branlant
authors.forename: Séverine
authors.initials: S
authors.lastname: Massenet
mesh_terms: D000483:Alleles; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D009154:Mutation; D020733:RNA, Small Cytoplasmic / Q000737:chemistry / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics; D018271:Signal Recognition Particle / Q000737:chemistry / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: C115990:7SL RNA; D000906:Antibodies; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; D055532:SMN Complex Proteins; D018271:Signal Recognition Particle; C405483:U1 small nuclear RNA; C405484:U2 small nuclear RNA