Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Détail de l'auteur
Auteur Gemma MOLINARO |
Documents disponibles écrits par cet auteur (1)
Faire une suggestion Affiner la recherche
Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP / Annie HIEN in Molecular Autism, 11 (2020)
[article]
Titre : Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP Type de document : Texte imprimé et/ou numérique Auteurs : Annie HIEN, Auteur ; Gemma MOLINARO, Auteur ; Botao LIU, Auteur ; Kimberly M. HUBER, Auteur ; Joel D. RICHTER, Auteur Article en page(s) : 78 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in TSC2 are the most common cause of tuberous sclerosis (TSC), a disorder with a high incidence of autism and intellectual disability. TSC2 regulates mRNA translation required for group 1 metabotropic glutamate receptor-dependent synaptic long-term depression (mGluR-LTD) and behavior, but the identity of mRNAs responsive to mGluR-LTD signaling is largely unknown. METHODS: We utilized Tsc2(+/-) mice as a mouse model of TSC and prepared hippocampal slices from these animals. We induced mGluR-LTD synaptic plasticity in slices and processed the samples for RNA-seq and ribosome profiling to identify differentially expressed genes in Tsc2(+/-) and following mGluR-LTD synaptic plasticity. RESULTS: Ribosome profiling reveals that in Tsc2(+/-) mouse hippocampal slices, the expression of several mRNAs was dysregulated: terminal oligopyrimidine (TOP)-containing mRNAs decreased, while FMRP-binding targets increased. Remarkably, we observed the opposite changes of FMRP binding targets in Fmr1(-/y) hippocampi. In wild-type hippocampus, induction of mGluR-LTD caused rapid changes in the steady-state levels of hundreds of mRNAs, many of which are FMRP targets. Moreover, mGluR-LTD failed to promote phosphorylation of eukaryotic elongation factor 2 (eEF2) in TSC mice, and chemically mimicking phospho-eEF2 with low cycloheximide enhances mGluR-LTD in TSC mice. CONCLUSION: These results suggest a molecular basis for bidirectional regulation of synaptic plasticity and behavior by TSC2 and FMRP. Our study also suggests that altered mGluR-regulated translation elongation contributes to impaired synaptic plasticity in Tsc2(+/-) mice. En ligne : http://dx.doi.org/10.1186/s13229-020-00384-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433
in Molecular Autism > 11 (2020) . - 78 p.[article] Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP [Texte imprimé et/ou numérique] / Annie HIEN, Auteur ; Gemma MOLINARO, Auteur ; Botao LIU, Auteur ; Kimberly M. HUBER, Auteur ; Joel D. RICHTER, Auteur . - 78 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 78 p.
Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in TSC2 are the most common cause of tuberous sclerosis (TSC), a disorder with a high incidence of autism and intellectual disability. TSC2 regulates mRNA translation required for group 1 metabotropic glutamate receptor-dependent synaptic long-term depression (mGluR-LTD) and behavior, but the identity of mRNAs responsive to mGluR-LTD signaling is largely unknown. METHODS: We utilized Tsc2(+/-) mice as a mouse model of TSC and prepared hippocampal slices from these animals. We induced mGluR-LTD synaptic plasticity in slices and processed the samples for RNA-seq and ribosome profiling to identify differentially expressed genes in Tsc2(+/-) and following mGluR-LTD synaptic plasticity. RESULTS: Ribosome profiling reveals that in Tsc2(+/-) mouse hippocampal slices, the expression of several mRNAs was dysregulated: terminal oligopyrimidine (TOP)-containing mRNAs decreased, while FMRP-binding targets increased. Remarkably, we observed the opposite changes of FMRP binding targets in Fmr1(-/y) hippocampi. In wild-type hippocampus, induction of mGluR-LTD caused rapid changes in the steady-state levels of hundreds of mRNAs, many of which are FMRP targets. Moreover, mGluR-LTD failed to promote phosphorylation of eukaryotic elongation factor 2 (eEF2) in TSC mice, and chemically mimicking phospho-eEF2 with low cycloheximide enhances mGluR-LTD in TSC mice. CONCLUSION: These results suggest a molecular basis for bidirectional regulation of synaptic plasticity and behavior by TSC2 and FMRP. Our study also suggests that altered mGluR-regulated translation elongation contributes to impaired synaptic plasticity in Tsc2(+/-) mice. En ligne : http://dx.doi.org/10.1186/s13229-020-00384-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433