title: The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression.
abstract: RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.
authors.affiliation: Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Hana
authors.initials: H
authors.lastname: Antonicka
authors.forename: Florin
authors.initials: F
authors.lastname: Sasarman
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nishimura
authors.forename: Vincent
authors.initials: V
authors.lastname: Paupe
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shoubridge
mesh_terms: D015152:Blotting, Northern; D045303:Cytochromes b / Q000378:metabolism; D058645:Denaturing Gradient Gel Electrophoresis; D042967:Electron Transport Complex I / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D034622:RNA Interference; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: C088356:GRSF1 protein, human; D024101:Mitochondrial Proteins; D009841:Oligonucleotides; D039102:Poly(A)-Binding Proteins; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D012313:RNA; D045303:Cytochromes b; C481838:MT-ND5 protein, human; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I