title: Preferential binding of a stable G3BP ribonucleoprotein complex to intron-retaining transcripts in mouse brain and modulation of their expression in the cerebellum.
abstract: Neuronal granules play an important role in the localization and transport of translationally silenced messenger ribonucleoproteins in neurons. Among the factors associated with these granules, the RNA-binding protein G3BP1 (stress-granules assembly factor) is involved in neuronal plasticity and is induced in Alzheimer's disease. We immunopurified a stable complex containing G3BP1 from mouse brain and performed high-throughput sequencing and cross-linking immunoprecipitation to identify the associated RNAs. The G3BP-complex contained the deubiquitinating protease USP10, CtBP1 and the RNA-binding proteins Caprin-1, G3BP2a and splicing factor proline and glutamine rich, or PSF. The G3BP-complex binds preferentially to transcripts that retain introns, and to non-coding sequences like 3'-untranslated region and long non-coding RNAs. Specific transcripts with retained introns appear to be enriched in the cerebellum compared to the rest of the brain and G3BP1 depletion decreased this intron retention in the cerebellum of G3BP1 knockout mice. Among the enriched transcripts, we found an overrepresentation of genes involved in synaptic transmission, especially glutamate-related neuronal transmission. Notably, G3BP1 seems to repress the expression of the mature Grm5 (metabotropic glutamate receptor 5) transcript, by promoting the retention of an intron in the immature transcript in the cerebellum. Our results suggest that G3BP is involved in a new functional mechanism to regulate non-coding RNAs including intron-retaining transcripts, and thus have broad implications for neuronal gene regulation, where intron retention is widespread.
authors: Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France.
authors: Sophie
authors: S
authors: Martin
authors: Computational Genomics Group Universitat Pompeu Fabra PRBB, Barcelona, Spain.|Laboratorio de Microbiología Aplicada y Biotecnología, Instituto Andino-Patagónico de Tecnologías Biológicas y Geoambientales (IPATEC), CONICET - UNComahue, Bariloche, Argentina.
authors: Nicolas
authors: N
authors: Bellora
authors: Computational Genomics Group Universitat Pompeu Fabra PRBB, Barcelona, Spain.
authors: Juan
authors: J
authors: González-Vallinas
authors: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Manuel
authors: M
authors: Irimia
authors: Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France.
authors: Karim
authors: K
authors: Chebli
authors: Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France.
authors: Marion
authors: M
authors: de Toledo
authors: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Monika
authors: M
authors: Raabe
authors: Computational Genomics Group Universitat Pompeu Fabra PRBB, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, Barcelona, Spain.
authors: Eduardo
authors: E
authors: Eyras
authors: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Henning
authors: H
authors: Urlaub
authors: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Ben J
authors: BJ
authors: Blencowe
authors: Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France. jamal.tazi@igmm.cnrs.fr.
authors: Jamal
authors: J
authors: Tazi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003594:Cytoplasmic Granules / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000075223:Poly-ADP-Ribose Binding Proteins; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D062085:RNA, Long Noncoding / Q000235:genetics; D014158:Transcription, Genetic; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D062085:RNA, Long Noncoding; C579090:USP10 protein, mouse; D012313:RNA; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D043222:Ubiquitin Thiolesterase; D004265:DNA Helicases; C492055:G3bp1 protein, mouse; D020365:RNA Helicases
keywords: G3BP; HITS-CLIP; cerebellum; retained intron; stress granules