title: A newcis-acting motif is required for the axonal SMN-dependent Anxa2 mRNA localization.
abstract: Spinal muscular atrophy (SMA) is caused by mutations and/or deletions of the survival motor neuron gene (SMN1). Besides its function in the biogenesis of spliceosomal snRNPs, SMN might possess a motor neuron specific role and could function in the transport of axonal mRNAs and in the modulation of local protein translation. Accordingly, SMN colocalizes with axonal mRNAs of differentiated NSC-34 motor neuron-like cells. We recently showed that SMN depletion gives rise to a decrease in the axonal transport of the mRNAs encoding Annexin A2 (Anxa2). In this work, we have characterized the structural features of the Anxa2 mRNA required for its axonal targeting by SMN. We found that a G-rich motif located near the 3'UTR is essential for axonal localization of the Anxa2 transcript. We also show that mutations in the motif sequence abolish targeting of Anxa2 reporter mRNAs in axon-like structures of differentiated NSC-34 cells. Finally, localization of both wild-type and mutated Anxa2 reporters is restricted to the cell body in SMN-depleted cells. Altogether, our studies show that this G-motif represents a novel and essential determinant for axonal localization of the Anxa2 mRNA mediated by the SMN complex.
authors.affiliation: IGMM, CNRS, Université Montpellier, Montpellier, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Rihan
authors.affiliation: IGMM, CNRS, Université Montpellier, Montpellier, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Antoine
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Physiopathologie du Retard Mental, 06560 Valbonne, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maurin
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Physiopathologie du Retard Mental, 06560 Valbonne, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.affiliation: IGMM, CNRS, Université Montpellier, Montpellier, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bordonné
authors.affiliation: IGMM, CNRS, Université Montpellier, Montpellier, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Soret
authors.affiliation: IGMM, CNRS, Université Montpellier, Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Rage
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D054856:G-Quadruplexes; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D059372:Nucleotide Motifs; D011485:Protein Binding; D021381:Protein Transport; D034443:RNA Transport; D012333:RNA, Messenger; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D017306:Annexin A2; D012333:RNA, Messenger; D055533:Survival of Motor Neuron 1 Protein
keywords: Anxa2; RNA transport; SMA; SMN; cis-acting motif