Developing a global understanding of the PRC and NuRD complexes in stem cell differentiation and in disease

Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegant TOR — Lehner and collaborator labs (2014)

Sergio Barberán-Soler, Laura Fontrodona, Anna Ribó, Ayelet T. Lamm, Camilla Iannone, Julián Cerón, Ben Lehner, Juan Valcárcel 

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.

Cell Reports (2014) 8: 1609-16   DOI: 10.1016/j.celrep.2014.08.016

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