title: Identification of novel nesprin-1 binding partners and cytoplasmic matrin-3 in processing bodies.
abstract: Nesprins are highly conserved spectrin repeat-containing scaffold proteins predominantly known to function at the nuclear envelope (NE). However, nesprin isoforms are emerging with localizations and scaffolding functions at sites away from the NE, suggesting their functions are more diverse than originally thought. In this study, we combined nesprin-1 coimmunoprecipitations with mass spectrometry to identify novel nesprin-1 binding partners for isoforms that localize to subcellular compartments beyond the NE. We show that one of these interactors, matrin-3 (matr3), localizes to mRNA processing bodies (PBs), where we have previously shown a nesprin-1 isoform to localize. Furthermore, we show that Matr3 is part of PB mRNP complexes, is a regulator of miRNA-mediated gene silencing, and possibly shuttles to stress granules in stressed cells. More importantly, we identify a new C-terminally truncated Matr3 isoform that is likely to be involved in these functions and PB localization. This study highlights several novel nesprin-1 binding partners and a new function and localization for Matr3 in cytoplasmic RNA granules.
authors.affiliation: Cardiovascular Division, King's College London, London SE5 9NU, United Kingdom dr15283@bristol.ac.uk.|Department of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Dipen
authors.initials: D
authors.lastname: Rajgor
authors.affiliation: Department of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Hanley
authors.affiliation: Cardiovascular Division, King's College London, London SE5 9NU, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Shanahan
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D017398:Alternative Splicing; D018929:Cell Culture Techniques; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C518587:MATR3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C415465:SYNE1 protein, human