{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:47:47Z","timestamp":1782280067961,"version":"3.54.5"},"posted":{"date-parts":[[2024,8,9]]},"group-title":"Developmental Biology","reference-count":96,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Sperm small RNAs have been implicated in intergenerational epigenetic inheritance of paternal environmental effects; however, their biogenesis and functions remain poorly understood. We previously identified a 5\u2019 fragment of tRNA-Valine-CAC-2 (tRFValCAC) as one of the most abundant small RNA in mature sperm. tRFValCAC is specifically enriched in sperm during post-testicular maturation in the epididymis, and we found that it is delivered to sperm from epididymis epithelial cells via extracellular vesicles. Here, we investigated the mechanistic basis of tRFValCAC delivery to sperm and its functions in the early embryo. We show that tRFValCAC interacts with an RNA binding protein, heterogeneous nuclear ribonucleoprotein A\/B (hnRNPAB), in the epididymis, and this interaction regulates the sorting and packing of tRFValCAC into extracellular vesicles. In the embryo, we found that tRFValCAC regulates early embryonic mRNA processing and splicing. Inhibition of tRFValCAC in preimplantation embryos altered the transcript abundance of genes involved in RNA splicing and mRNA processing. Importantly, tRFValCAC-inhibited embryos showed altered mRNA splicing, including alternative splicing of various splicing factors and genes important for proper preimplantation embryonic development. Finally, we find that inhibition of tRFValCAC in zygotes delayed preimplantation embryonic development. Together, our results reveal a novel function of a sperm-enriched tRF in regulating alternating splicing and preimplantation embryonic development and shed light on the mechanism of sperm small RNA-mediated epigenetic inheritance.<\/jats:p>","DOI":"10.1101\/2024.08.08.607197","type":"posted-content","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T17:40:19Z","timestamp":1723225219000},"source":"Crossref","is-referenced-by-count":5,"title":["A sperm-enriched 5\u2019fragment of tRNA-Valine regulates preimplantation embryonic transcriptome and development"],"prefix":"10.64898","author":[{"given":"Simeiyun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Katzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasna","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024083004101073000_2024.08.08.607197v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2010.01.008"},{"key":"2024083004101073000_2024.08.08.607197v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb2603s109"},{"issue":"5","key":"2024083004101073000_2024.08.08.607197v2.3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41592-023-01813-2","article-title":"A standardized ontology for naming tRNA-derived RNAs based on molecular origin","volume":"20","year":"2023","journal-title":"Nat Methods"},{"key":"2024083004101073000_2024.08.08.607197v2.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad6780"},{"key":"2024083004101073000_2024.08.08.607197v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.06.023"},{"key":"2024083004101073000_2024.08.08.607197v2.6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1837609"},{"key":"2024083004101073000_2024.08.08.607197v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.09.001"},{"issue":"4","key":"2024083004101073000_2024.08.08.607197v2.8","first-page":"1638","article-title":"tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression","volume":"5","year":"2015","journal-title":"Life (Basel"},{"key":"2024083004101073000_2024.08.08.607197v2.9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa657"},{"key":"2024083004101073000_2024.08.08.607197v2.10","doi-asserted-by":"publisher","DOI":"10.4161\/rna.24285"},{"key":"2024083004101073000_2024.08.08.607197v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.06.022"},{"key":"2024083004101073000_2024.08.08.607197v2.12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa336"},{"key":"2024083004101073000_2024.08.08.607197v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.008"},{"key":"2024083004101073000_2024.08.08.607197v2.14","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/260909"},{"key":"2024083004101073000_2024.08.08.607197v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.09.010"},{"key":"2024083004101073000_2024.08.08.607197v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.062"},{"key":"2024083004101073000_2024.08.08.607197v2.17","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00267"},{"key":"2024083004101073000_2024.08.08.607197v2.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206761110"},{"key":"2024083004101073000_2024.08.08.607197v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.124"},{"key":"2024083004101073000_2024.08.08.607197v2.20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac022"},{"key":"2024083004101073000_2024.08.08.607197v2.21","unstructured":"Kumar, P ., Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. 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