Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline


Watanabe Toshiaki,Cheng Ee-chun,Zhong Mei,Lin Haifan


The eukaryotic genome has vast intergenic regions containing transposons, pseudogenes, and other repetitive sequences. They produce numerous long noncoding RNAs (lncRNAs) and Piwi-interacting RNAs (piRNAs), yet the functions of the vast intergenic regions remain largely unknown. Mammalian piRNAs are abundantly expressed from the spermatocyte to round spermatid stage, coinciding with the widespread expression of lncRNAs in these cells. Here, we show that piRNAs derived from transposons and pseudogenes mediate the degradation of a large number of mRNAs and lncRNAs in mouse late spermatocytes. In particular, they have a large impact on the lncRNA transcriptome, as a quarter of lncRNAs expressed in late spermatocytes are up-regulated in mice deficient in the piRNA pathway. Furthermore, our genomic and in vivo functional analyses reveal that retrotransposon sequences in the 3′ UTR of mRNAs are targeted by piRNAs for degradation. Similarly, the degradation of spermatogenic cell-specific lncRNAs by piRNAs is mediated by retrotransposon sequences. Moreover, we show that pseudogenes regulate mRNA stability via the piRNA pathway. The degradation of mRNAs and lncRNAs by piRNAs requires PIWIL1 (also known as MIWI) and, at least in part, depends on its slicer activity. Together, these findings reveal the presence of a highly complex and global RNA regulatory network mediated by piRNAs with retrotransposons and pseudogenes as regulatory sequences.



Connecticut Stem Cell Research


Cold Spring Harbor Laboratory



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