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           <jats:p>PIWI proteins and PIWI-interacting RNAs (piRNAs) are specifically expressed in animal germlines and play essential roles during gametogenesis in animals. The primary function of PIWI\/piRNAs is known to silence transposable elements for protecting genome integrity in animal germlines, while their roles beyond silencing transposons are also documented by us and others. In particular, we show that mouse PIWIL1 (MIWI)\/piRNAs play a dual role in regulating protein-coding genes in mouse spermatids through interacting with different protein factors in a developmental stage-dependent manner, including translationally activating a subset of AU-rich element-containing mRNAs in round spermatids and inducing massive mRNA degradation in late spermatids. We further show that MIWI is eliminated through the ubiquitin-26S proteasome pathway during late spermiogenesis. By exploring the biological function of MIWI ubiquitination by APC\/C, we identified ubiquitination-deficient mutations in human PIWIL1 of infertile men and further established their causative role in male infertility in mouse model, supporting PIWIL1 as a human male infertility-relevant gene. Additionally, we reported that PIWIL1, aberrantly induced in human tumors, functions as an oncoprotein in a piRNA-independent manner in cancer cells. In the current review, we summarize our latest findings regarding the roles and mechanisms of PIWIL1 and piRNAs in mouse spermatids and human diseases, and discuss the related works in the field.<\/jats:p>","DOI":"10.1093\/biolre\/ioac073","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T11:48:02Z","timestamp":1649677682000},"page":"101-108","source":"Crossref","is-referenced-by-count":23,"title":["Noncanonical functions of PIWIL1\/piRNAs in animal male germ cells and human diseases"],"prefix":"10.1093","volume":"107","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai, China"},{"name":"School of Life Science , Hangzhou Institute for Advanced Study, , Hangzhou China"},{"name":"University of Chinese Academy of Sciences , Hangzhou Institute for Advanced Study, , Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Tao","family":"Gou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo-Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai, China"},{"name":"School of Life Science , Hangzhou Institute for Advanced Study, , Hangzhou China"},{"name":"University of Chinese Academy of Sciences , Hangzhou Institute for Advanced Study, , Hangzhou China"},{"name":"School of Life Science and Technology, Shanghai Tech University , Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"2022072511584941100_ref1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41576-018-0073-3","article-title":"PIWI-interacting RNAs: small RNAs with big functions","volume":"20","author":"Ozata","year":"2019","journal-title":"Nat Rev Genet"},{"key":"2022072511584941100_ref2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev-genet-120417-031441","article-title":"piRNA-guided genome defense: from biogenesis to silencing","volume":"52","author":"Czech","year":"2018","journal-title":"Annu Rev Genet"},{"key":"2022072511584941100_ref3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-biochem-060614-034258","article-title":"PIWI-interacting RNA: its biogenesis and 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