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In addition, siRNAs are produced from a broad range of endogenous dsRNAs in\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  . However, beyond the impacts of siRNAs derived from a handful of hairpin RNAs, the regulatory potential of most endo-siRNAs has been unknown. Here, we report that RNAi is far more potent in the close sister species\n                  <jats:italic>Drosophila simulans<\/jats:italic>\n                  . Consequently, endo-siRNAs repress less than a dozen transcripts in\n                  <jats:italic>D. melanogaster<\/jats:italic>\n                  , but hundreds of mRNAs in\n                  <jats:italic>D. simulans<\/jats:italic>\n                  testis. These regulatory interactions occur in cis (between pairs of bidirectionally transcribed loci), as well as in trans (between genomically unlinked siRNA-target pairs). We establish the molecular determinants of productive gene repression by siRNAs\n                  <jats:italic>in vivo<\/jats:italic>\n                  , including cleavage in trans via\n                  <jats:underline>&gt;<\/jats:underline>\n                  16-nt contiguous complementarity. Our data indicate that\n                  <jats:italic>D. simulans<\/jats:italic>\n                  spermatogenesis requires repression of numerous host mRNAs by endo-siRNAs. More generally, we reveal unexpectedly fast-evolving and broad regulatory impacts of endogenous RNAi in the male germline.\n                <\/jats:p>","DOI":"10.64898\/2026.05.18.725984","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:00:20Z","timestamp":1779163220000},"source":"Crossref","is-referenced-by-count":0,"title":["Divergent regulatory impacts of endogenous siRNAs on host mRNAs in testis of closely related species"],"prefix":"10.64898","author":[{"given":"Mina","family":"Zamani","sequence":"first","affiliation":[{"name":"Department of Biology, New York University, 29 Washington Place, Rm 753, New York, NY 10003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiya","family":"Jarva","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan Kettering Institute, New York, NY, 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Moukheiber","sequence":"additional","affiliation":[{"name":"Department of Biology, New York University, 29 Washington Place, Rm 753, New York, NY 10003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava","family":"Kloss-Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biology, New York University, 29 Washington Place, Rm 753, New York, NY 10003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandagopal","family":"Ajaykumar","sequence":"additional","affiliation":[{"name":"Department of Biology, New York University, 29 Washington Place, Rm 753, New York, NY 10003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan Kettering Institute, New York, NY, 10065 USA"},{"name":"Weill Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Chalouh-Hara","sequence":"additional","affiliation":[{"name":"Yeshiva University, New York, NY 10033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avishye","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"Yeshiva University, New York, NY 10033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-5271","authenticated-orcid":false,"given":"Josefa","family":"Steinhauer","sequence":"additional","affiliation":[{"name":"Yeshiva University, New York, NY 10033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-5851","authenticated-orcid":false,"given":"Eric C.","family":"Lai","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Sloan Kettering Institute, New York, NY, 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1719-043X","authenticated-orcid":false,"given":"Ildar","family":"Gainetdinov","sequence":"additional","affiliation":[{"name":"Department of Biology, New York University, 29 Washington Place, Rm 753, New York, NY 10003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052107000734000_2026.05.18.725984v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00818-9"},{"key":"2026052107000734000_2026.05.18.725984v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.006"},{"key":"2026052107000734000_2026.05.18.725984v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00611-y"},{"key":"2026052107000734000_2026.05.18.725984v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0073-3"},{"key":"2026052107000734000_2026.05.18.725984v1.5","doi-asserted-by":"crossref","unstructured":"Wang, X. , Ramat, A. , Simonelig, M. & Liu, M.-F . 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