title: Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR.
abstract: Many eukaryotic genes contain embedded antisense transcripts and repetitive sequences of unknown function. We report that male germline-specific expression of an antisense transcript contained in an intron of C. elegans Target of Rapamycin (TOR, let-363) is associated with (1) accumulation of endo-small interfering RNAs (siRNAs) against an embedded Helitron transposon and (2) activation of an alternative 3' splice site of TOR. The germline-specific Argonaute proteins PRG-1 and CSR-1, which participate in self/nonself RNA recognition, antagonistically regulate the generation of these endo-siRNAs, TOR mRNA levels, and 3' splice-site selection. Supply of exogenous double-stranded RNA against the region of sense/antisense overlap reverses changes in TOR expression and splicing and suppresses the progressive multigenerational sterility phenotype of prg-1 mutants. We propose that recognition of a "nonself" intronic transposon by endo-siRNAs/the piRNA system provides physiological regulation of expression and alternative splicing of a host gene that, in turn, contributes to the maintenance of germline function across generations.
authors.affiliation: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barberán-Soler
authors.affiliation: Department of Cancer and Human Molecular Genetics, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontrodona
authors.affiliation: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Ribó
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Ayelet T
authors.initials: AT
authors.lastname: Lamm
authors.affiliation: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Camilla
authors.initials: C
authors.lastname: Iannone
authors.affiliation: Department of Cancer and Human Molecular Genetics, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Cerón
authors.affiliation: Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain; EMBL-CRG Systems Biology Program, CRG, Dr. Aiguader 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain. Electronic address: ben.lehner@crg.eu.
authors.forename: Ben
authors.initials: B
authors.lastname: Lehner
authors.affiliation: Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain. Electronic address: juan.valcarcel@crg.eu.
authors.forename: Juan
authors.initials: J
authors.lastname: Valcárcel
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D005854:Germ Cells; D008297:Male; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016372:RNA, Antisense / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C530363:PRG-1 protein, C elegans; D020033:Protein Isoforms; D016372:RNA, Antisense; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases