C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts.
Piwi Argonautes and Piwi-interacting RNAs (piRNAs) mediate genome defense by targeting transposons. However, many piRNA species lack obvious sequence complementarity to transposons or other loci; only one C. elegans transposon is a known piRNA target. Here, we show that, in mutants lacking the Piwi Argonaute PRG-1 (and consequently its associated piRNAs/21U-RNAs), many silent loci in the germline exhibit increased levels of mRNA expression with a concomitant depletion of RNA-dependent RNA polymerase (RdRP)-derived secondary small RNAs termed 22G-RNAs. Sequences depleted of 22G-RNAs are proximal to potential target sites that base pair imperfectly but extensively to 21U-RNAs. We show that PRG-1 is required to initiate, but not to maintain, silencing of transgenes engineered to contain complementarity to endogenous 21U-RNAs. Our findings support a model in which C. elegans piRNAs utilize their enormous repertoire of targeting capacity to scan the germline transcriptome for foreign sequences, while endogenous germline-expressed genes are actively protected from piRNA-induced silencing.
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Heng-Chi
HC
Lee
Weifeng
W
Gu
Masaki
M
Shirayama
Elaine
E
Youngman
Darryl
D
Conte
Craig C
CC
Mello
D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing; D049751:Genome, Helminth; D005854:Germ Cells; D018510:RNA, Helminth / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*
D060565:Argonaute Proteins; D018510:RNA, Helminth; D034741:RNA, Small Interfering