title: Genome-wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization.
abstract: Spinal muscular atrophy is a neuromuscular disease resulting from mutations in the SMN1 gene, which encodes the survival motor neuron (SMN) protein. SMN is part of a large complex that is essential for the biogenesis of spliceosomal small nuclear RNPs. SMN also colocalizes with mRNAs in granules that are actively transported in neuronal processes, supporting the hypothesis that SMN is involved in axonal trafficking of mRNPs. Here, we have performed a genome-wide analysis of RNAs present in complexes containing the SMN protein and identified more than 200 mRNAs associated with SMN in differentiated NSC-34 motor neuron-like cells. Remarkably, ~30% are described to localize in axons of different neuron types. In situ hybridization and immuno-fluorescence experiments performed on several candidates indicate that these mRNAs colocalize with the SMN protein in neurites and axons of differentiated NSC-34 cells. Moreover, they localize in cell processes in an SMN-dependent manner. Thus, low SMN levels might result in localization deficiencies of mRNAs required for axonogenesis.
authors.forename: Florence
authors.initials: F
authors.lastname: Rage
authors.forename: Nawal
authors.initials: N
authors.lastname: Boulisfane
authors.forename: Khalil
authors.initials: K
authors.lastname: Rihan
authors.forename: Henry
authors.initials: H
authors.lastname: Neel
authors.forename: Thierry
authors.initials: T
authors.lastname: Gostan
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Rémy
authors.initials: R
authors.lastname: Bordonné
authors.forename: Johann
authors.initials: J
authors.lastname: Soret
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D016678:Genome; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051151:Selenoprotein W / Q000235:genetics / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051151:Selenoprotein W; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D003576:Electron Transport Complex IV
keywords: SMN; axonal mRNAs; mRNA localization; spinal muscular atrophy