Abstract
Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon silencing and regulation of gametogenesis. The production of mature piwi-interacting RNAs requires a critical step of trimming piwi-interacting RNA intermediates to achieve optimally sized piwi-interacting RNAs. The poly(A)-specific ribonuclease family deadenylase PNLDC1 is implicated in piwi-interacting RNA trimming in silkworms. The physiological function of PNLDC1 in mammals remains unknown. Using Pnldc1-deficient mice, here we show that PNLDC1 is required for piwi-interacting RNA biogenesis, transposon silencing, and spermatogenesis. Pnldc1 mutation in mice inhibits piwi-interacting RNA trimming and causes accumulation of untrimmed piwi-interacting RNA intermediates with 3′ end extension, leading to severe reduction of mature piwi-interacting RNAs in the testis. Pnldc1 mutant mice exhibit disrupted LINE1 retrotransposon silencing and defect in spermiogenesis. Together, these results define PNLDC1 as a mammalian piwi-interacting RNA biogenesis factor that protects the germline genome and ensures normal sperm production in mice.
Highlights
Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon silencing and regulation of gametogenesis
The poly(A)-specific ribonuclease (PARN) group exonucleases, including poly(A)-specific ribonuclease-like domain containing 1 (PNLDC1) and PARN, belong to a family of deadenylases that are responsible for the removal of the 3′ poly(A) tails of messenger RNA (mRNA) to control mRNA decay[30, 33,34,35]
Two elegant studies demonstrate a novel function of the 3′–5′ exonuclease activity of PNLDC1 and PARN in Piwi-interacting RNAs (piRNAs) trimming, a function beyond poly (A) mRNA turnover[12, 13]
Summary
Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon silencing and regulation of gametogenesis. Using Pnldc1-deficient mice, here we show that PNLDC1 is required for piwi-interacting RNA biogenesis, transposon silencing, and spermatogenesis. Pnldc[1] mutant mice exhibit disrupted LINE1 retrotransposon silencing and defect in spermiogenesis Together, these results define PNLDC1 as a mammalian piwi-interacting RNA biogenesis factor that protects the germline genome and ensures normal sperm production in mice. The related protein, poly(A)-specific ribonuclease-like domain containing 1 (PNLDC1), identified as a TDRKH/Papi interacting protein, is the trimmer for pre-piRNA 3′ end trimming in silkworm[13]. We show that PNLDC1 is required for mammalian piRNA 3′ trimming in vivo and is essential for transposon silencing and spermatogenesis in mice. F The timeline of mouse spermatogenesis with red crosses representing the arrested spermatogenic stages in Pnldc1Mut and Tdrkh KO testes a LINE1 ORF1 In situ hybridization Mut b 20 μm. f The timeline of mouse spermatogenesis with red crosses representing the arrested spermatogenic stages in Pnldc1Mut and Tdrkh KO testes a LINE1 ORF1 In situ hybridization Mut b
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