4 research outputs found
Ympäristön ja elintapojen vaikutus miesten sukusolujen epigenomiin
Elintavoista ja ympäristöaltistuksista johtuvat terveyden häiriöt muodostavat suuren ongelman teollistuneessa länsimaisessa nyky-yhteiskunnassa. Näihin lukeutuvat myös miesten lisääntymisterveyden ongelmat, kuten siittiöiden laadun ja määrän laskeminen, joiden yhtenä tärkeänä aiheuttaja pidetään ympäristötekijöitä. Epigeneettisellä geenisäätelyllä on merkittävä rooli hedelmöityskykyisen siittiön muodostuksessa. Sukusolujen epigenomi on altis ympäristön vaikutuksille, ja on selvää, että epigenomin häiriöillä voi olla vakavia seurauksia siittiön muodostukseen. Sukusolujen epigenomin häiriöillä saattaa olla myös kauaskantoisempia vaikutuksia aina seuraaviin sukupolviin saakka, sillä eläinkokeilla on osoitettu, että tieto hankitusta ominaisuudesta voi siirtyä jälkeläiselle siittiöiden epigeneettisen tiedon välityksellä
SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3 ' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.Peer reviewe
SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3 ' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.Peer reviewe
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SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility