piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis.

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Goh, Wee Siong Sho 
Falciatori, Ilaria 
Tam, Oliver H 
Burgess, Ralph 
Meikar, Oliver 

MIWI catalytic activity is required for spermatogenesis, indicating that piRNA-guided cleavage is critical for germ cell development. To identify meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing a human meiotic piRNA cluster. This triggered a spermatogenesis defect by inappropriately targeting the piRNA machinery to mouse mRNAs essential for germ cell development. Analysis of such de novo targets revealed a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage of genic targets began at the pachytene stage and resulted in progressive repression through meiosis, driven at least in part via the ping-pong cycle. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells.

MIWI, RNA cleavage, exogenous piRNAs, pachytene piRNAs, ping-pong cycle, spermatogenesis defect, Animals, DNA Transposable Elements, Gene Expression Regulation, Developmental, Gene Silencing, Humans, Infertility, Male, Male, Meiosis, Mice, Open Reading Frames, Pachytene Stage, RNA, Small Interfering, Spermatogenesis, Testis
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Genes Dev
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Cold Spring Harbor Laboratory
This work was supported by the National Institutes of Health R37 grant GM062534-14 to G.J.H. iTRAQ was performed with assistance from the Cold Spring Harbor Laboratory Proteomics Shared Resource, which is supported by Cancer Center support grant 5P30CA045508. W.S.S.G. is a McClintock Fellow of the Watson School of Biological Sciences and is supported by the NSS Scholarship from the Agency for Science, Technology and Research, Singapore. O.H.T. is supported by a fellowship of the Human Frontier Science Program. R.B. is supported by the Starr Centennial Scholarship from the Watson School of Biological Sciences. G.J.H. is a Howard Hughes Medical Institute Investigator.