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| 1 | A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis显示文摘Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation of gene expression. Here we identify that the zygotene to pachytene transit!on is not only associated with the resumption of transcription but also a wave of programmed mRNA degradation that is essential for meiotic progress!on. We explored whether terminal uridydyl transferase 4-(TUT4-) or TUT7-mediated 3' mRNA uridylation contributes to this wave of mRNA degradation during pachynema. Indeed, both TUT4 and TUT7 are expressed throughout most of spermatogenesis, however, loss of either TUT4 or TUT7 does not have any major impact upon spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, while conditional gene targeting revealed an essential role for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of miRNA, piRNA and mRNA 31 uridylation. Although this reduction does not greatly alter miRNA or piRNA expression, TUT4/7-mediated uridylation is required for the clearanee of many zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3Z UTRs with length-adjusted enrichment for AU-rich elements. We also observed these features in TUT4/7-regulated maternal transcripts whose dosage was recently shown to be essential for sculpting a functional maternal transcriptome and meiosis. Therefore, mRNA 3Z uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we have identified a novel requirement for 3' uridylation-programmed zygotene mRNA clearanee in pachytene spermatocytes that is essential for male meiotic progression. | Marcos Morgan Yuka Kabayama Christian Much Ivayla Ivanova Monica Di Giacomo Tatsiana Auchynnikava Jack Michael Monahan Dimitrios Michael Vitsios Lina Vasiliauskaite Stefano Comazzetto Juri Rappsilber Robin Campbell Allshire Bo Torben Porse Anton James Enright Donal O'Carroll | 2019 | Cell Research2019，29，3： | 1 |
| 2 | The testis-specifically expressed gene Trim69 is not essential for fertility in mice显示文摘Protein ubiquitination is essential for diverse cellular functions including spermatogenesis.The tripartite motif(TRIM)family proteins,most of which have E3 ubiquitin ligase activity,are highly conserved in mammals.They are involved in important cellular processes such as embryonic development,immunity,and fertility.Our previous studies indicated that Trim69,a testis-specific expressed TRIM family gene,potentially participates in the spermatogenesis by mediating testicular cells apoptosis.In this study,we investigated the biological functions of Trim69 in male mice by established Trim69 knockout mice with CRISPR/Cas9 genomic editing technology.Here,we reported that the male Trim69 knockout mice had normal fertility.The adult knockout mice have shown that the appearance of testes,testis/body weight ratios,testicular histomorphology,and the number and quality of sperm were consistent with wild-type mice.These results indicated that the E3 ubiquitin ligase protein Trim69 was not essential for male mouse fertility,and it might be compensated by other TRIM family members such as Trim58 in Trim69-deficiency testis.This study would help to elucidate the functions of tripartite motif protein family and the regulation of spermatogenesis. | Xi He Wenxiu Xie Huiling Li Yiqiang Cui Ya Wang Xuejiang Guo Jiahao Sha | 2021 | The Journal of Biomedical Research2021，35，1： | 0 |
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