Understanding biogenesis and function of mRNA-derived PIWI-interacting RNAs in the male mouse germline

Diplôme Master Understanding biogenesis and function of mRNA-derived PIWI-interacting RNAs in the male mouse germline eng 2025-08-28 author Darques Marcelle Vanora 928004 director Wu Pei-Hsuan 978012 Département de médecine génétique et développement (GEDEV) 45 PIWI-interacting RNAs (piRNAs) are small non-coding RNAs (small RNAs) specific to the animal germline. In mice, they play a crucial role in male fertility, spermatogenesis, and sperm function. Three classes of mouse piRNAs are expressed at different developmental stages in postnatal testes: pre-pachytene, pachytene, and hybrid piRNAs. Pre-pachytene and pachytene piRNAs were named for the onset of their expression before and at meiosis in spermatogenesis, respectively. By contrast, mouse hybrid piRNAs come from 30 genomic loci and share developmental expression features of both pachytene and pre-pachytene piRNAs— beginning at 10.5 dpp and continuing thereafter. Notably, 25 of these 30 hybrid piRNA-producing loci produce piRNAs from the 3′ untranslated region (3′UTR) of mRNAs. While the role of pachytene piRNAs in male fertility is well established, little is known about the biogenesis and function of hybrid piRNAs. We aim to understand these bifunctional piRNA-producing mRNAs by studying the dynamics of 3′UTR length and its correlation with transcript abundance and piRNA production efficiency. In this study, we showed that all reported Asb1 and Kctd7 mRNA 3′UTR isoforms are expressed in both mouse liver and testes, with a striking testis-specific enrichment and developmental regulation during spermatogenesis. We further demonstrated that these 3′UTR isoforms give rise to testis-specific and also developmentally regulated piRNAs (pi-Asb1 and pi-Kctd7), which are partially loaded into PIWI proteins. At the protein level, ASB1 is consistently expressed during spermatogenesis and localizes to the cytoplasm of spermatocytes and early spermatids, highlighting a potential role in germ cell differentiation. Together, our results suggest that ASB1 plays a role in spermatocyte differentiation, while KCTD7 may be regulated via piRNA-mediated mechanisms. Our work highlights the testis as a unique system where 3′UTR isoform dynamics, piRNA biogenesis, and protein expression intersect to regulate germ cell development. PiRNAs Male fertility Spermatogenesis 3′ untranslated region ASB1 KCTD7 Dewey 590 Dewey 576.5 Master en biologie 135 Département de médecine génétique et développement 21D 44 Département de génétique et évolution 162 false 1385 Fonction et mécanisme des petits ARN non codants germinaux dans le sperme et les embryons 1037 97dfa723-793a-43c9-a2b8-9e0ceb37334e Master thesis Restricted 20250825_MSc_thesis_MVD.pdf 2731244 application/pdf ea4576dd915d004be9cb12d0e0f8c7a1f2b594c00c853ee7d82bbce7724854eb restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté des sciences / Section de biologie / Département de génétique et évolution

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Understanding biogenesis and function of mRNA-derived PIWI-interacting RNAs in the male mouse germline				2025	30	3

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Darques, Marcelle Vanora

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