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Cell Rep. 2014 Sep 25;8(6):1609-1616. doi: 10.1016/j.celrep.2014.08.016. Epub 2014 Sep 15.

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

Author information

1
Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain.
2
Department of Cancer and Human Molecular Genetics, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
3
Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
4
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.
5
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.
6
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.

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.

PMID:
25220461
DOI:
10.1016/j.celrep.2014.08.016
[Indexed for MEDLINE]
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