Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR

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• dc.contributor.author Barberán-Soler, Sergio
• dc.contributor.author Fontrodona, Laura
• dc.contributor.author Ribó Rubio, Anna
• dc.contributor.author Lamm, Ayelet T.
• dc.contributor.author Iannone, Camilla, 1984-
• dc.contributor.author Cerón, Julián
• dc.contributor.author Lehner, Ben, 1978-
• dc.contributor.author Valcárcel, J. (Juan)
• dc.date.accessioned 2023-06-27T06:07:33Z
• dc.date.available 2023-06-27T06:07:33Z
• dc.date.issued 2014
• dc.description Includes supplementary materials for the online appendix.
• dc.description.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.
• dc.description.sponsorship We thank A. Fire, S. Ahmed, and E. Miska for sharing information and helpful discussions, members of our laboratories for critical feedback, the Caenorhabditis Genetics Center (CGC) for providing strains, Matthew Ragle for collection of sperm samples, Alan Zahler for assistance and critical feedback, and Montserrat Porta de la Riva for technical assistance. S.B.-S. was supported by an EMBO postdoctoral fellowship. A.T.L. is a Taub Fellow, supported by the Taub Foundation. J.C. is a Miguel Servet Junior Investigator. Work in J.V.’s lab is supported by Fundación Botín, Consolider RNAREG and Ministerio de Economía y Competitividad (MINECO). Work in B.L.’s lab is supported by the European Research Council (ERC), MINECO Plan Nacional grants BFU2008-00365 and BFU2011-26206, ERASysBio+ ERANET project EUI2009-04059 GRAPPLE, the EMBO Young Investigator Program, EU Framework 7 project 277899 4DCellFate, the AXA Research Fund, and the EMBL/CRG Systems Biology Program. Support from the CRG Genomics Facility is also acknowledged.
• dc.format.mimetype application/pdf
• dc.identifier.citation Barberán-Soler S, Fontrodona L, Ribó A, Lamm AT, Iannone C, Cerón J, et al. Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR. Cell Reports. 2014 Sep 25;8(6):1609-16. DOI: 10.1016/j.celrep.2014.08.016
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2014.08.016
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/57348
• dc.language.iso eng
• dc.publisher Cell Press
• dc.relation.ispartof Cell Reports. 2014 Sep 25;8(6):1609-16
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-00365
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
• dc.rights This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
• dc.subject.other Cromatina
• dc.subject.other Citoplasma
• dc.subject.other Cèl·lules
• dc.subject.other Cèl·lules humanes -- Cultius
• dc.title Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion