title: Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.
abstract: Genes coding for members of the Sm-like (LSm) protein family are conserved through evolution from prokaryotes to humans. These proteins have been described as forming homo- or heterocomplexes implicated in a broad range of RNA-related functions. To date, the nuclear LSm2-8 and the cytoplasmic LSm1-7 heteroheptamers are the best characterized complexes in eukaryotes. Through a comprehensive functional study of the LSm family members, we found that lsm-1 and lsm-3 are not essential for C. elegans viability, but their perturbation, by RNAi or mutations, produces defects in development, reproduction, and motility. We further investigated the function of lsm-1, which encodes the distinctive protein of the cytoplasmic complex. RNA-seq analysis of lsm-1 mutants suggests that they have impaired Insulin/IGF-1 signaling (IIS), which is conserved in metazoans and involved in the response to various types of stress through the action of the FOXO transcription factor DAF-16. Further analysis using a DAF-16::GFP reporter indicated that heat stress-induced translocation of DAF-16 to the nuclei is dependent on lsm-1. Consistent with this, we observed that lsm-1 mutants display heightened sensitivity to thermal stress and starvation, while overexpression of lsm-1 has the opposite effect. We also observed that under stress, cytoplasmic LSm proteins aggregate into granules in an LSM-1-dependent manner. Moreover, we found that lsm-1 and lsm-3 are required for other processes regulated by the IIS pathway, such as aging and pathogen resistance.
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain Université Bordeaux, IECB, Laboratoire ARNA, F-33600 Pessac, France INSERM, U869, Laboratoire ARNA, F-33000 Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Cornes
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain C. elegans Core Facility, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Porta-De-La-Riva
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Aristizábal-Corrales
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), CSIC - UPO - Junta de Andalucía, Sevilla 41013, Spain.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Brokate-Llanos
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: García-Rodríguez
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Ertl
authors.affiliation: Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d'Hebron Research Institute, Universidad Autónoma de Barcelona, Barcelona 08035, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontrodona
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Kadri
authors.initials: K
authors.lastname: Reis
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Johnsen
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Baillie
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), CSIC - UPO - Junta de Andalucía, Sevilla 41013, Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Muñoz
authors.affiliation: TransgeneOmics Unit, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
authors.forename: Mihail
authors.initials: M
authors.lastname: Sarov
authors.affiliation: Université Bordeaux, IECB, Laboratoire ARNA, F-33600 Pessac, France INSERM, U869, Laboratoire ARNA, F-33000 Bordeaux, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Dupuy
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Cerón
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020043:Genes, Essential; D006358:Hot Temperature; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; C000602639:LSm-1 protein, C elegans; C000602640:LSm-3 protein, C elegans; D016601:RNA-Binding Proteins; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I
keywords: Caenorhabditis elegans; LSM, daf-16; P bodies; stress granules; stress response