title: Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling cellular distribution of Like-Sm proteins.
abstract: Processing bodies (P-bodies) are dynamic cytoplasmic structures involved in mRNA degradation, but the mechanism that governs their formation is poorly understood. In this paper, we address a role of Like-Sm (LSm) proteins in formation of P-bodies and provide evidence that depletion of nuclear LSm8 increases the number of P-bodies, while LSm8 overexpression leads to P-body loss. We show that LSm8 knockdown causes relocalization of LSm4 and LSm6 proteins to the cytoplasm and suggest that LSm8 controls nuclear accumulation of all LSm2-7 proteins. We propose a model in which redistribution of LSm2-7 to the cytoplasm creates new binding sites for other P-body components and nucleates new, microscopically visible structures. The model is supported by prolonged residence of two P-body proteins, DDX6 and Ago2, in P-bodies after LSm8 depletion, which indicates stronger interactions between these proteins and P-bodies. Finally, an increased number of P-bodies has negligible effects on microRNA-mediated translation repression and nonsense mediated decay, further supporting the view that the function of proteins localized in P-bodies is independent of visible P-bodies.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Novotny
authors.forename: Katerina
authors.initials: K
authors.lastname: Podolská
authors.forename: Michaela
authors.initials: M
authors.lastname: Blazíková
authors.forename: Leos Shivaya
authors.initials: LS
authors.lastname: Valásek
authors.forename: Petr
authors.initials: P
authors.lastname: Svoboda
authors.forename: David
authors.initials: D
authors.lastname: Stanek
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D063211:N-Terminal Acetyltransferase C / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000378:metabolism / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism
chemical_list: D001324:Autoantigens; C117009:NAA38 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C465663:TNRC6A protein, human; D063211:N-Terminal Acetyltransferase C; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases