title: The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules.
abstract: RNA localization pathways direct numerous mRNAs to distinct subcellular regions and affect many physiological processes. In one such pathway the tumor-suppressor protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions, forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. Labeling of newly synthesized proteins revealed that Fus promotes translation preferentially within protrusions. Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules. We show that overexpression or mutation of Fus results in formation of granules, which preferentially recruit APC-RNPs. Remarkably, these granules are not translationally silent. Instead, APC-RNP transcripts are translated within cytoplasmic Fus granules. These results unexpectedly show that translation can occur within stress-like granules. Importantly, they identify a new local function for cytoplasmic Fus with implications for ALS pathology.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Kyota
authors.initials: K
authors.lastname: Yasuda
authors.forename: Huaye
authors.initials: H
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Loiselle
authors.forename: Timothy
authors.initials: T
authors.lastname: Haystead
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
authors.forename: Stavroula
authors.initials: S
authors.lastname: Mili
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000502:physiology*; D012261:Ribonucleoproteins / Q000378:metabolism / Q000502:physiology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012333:RNA, Messenger; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins