RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis.
RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis.
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RNA聚合酶II的停顿在精子发生过程中对于适当的基因表达和减数分裂的完成是必不可少的。
DOI：
10.1038/s41467-024-45177-3
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发表时间：
2024-01-29
影响因子：
16.6
通讯作者：
Reddi, Prabhakara P.
中科院分区：
文献类型：
--
作者：
Kaye, Emily G.;Basavaraju, Kavyashree;Nelson, Geoffrey M.;Zomer, Helena D.;Roy, Debarun;Joseph, Irene Infancy;Rajabi-Toustani, Reza;Qiao, Huanyu;Adelman, Karen;Reddi, Prabhakara P.
男性生殖细胞的发育需要以细胞类型和阶段特异性的方式精确调节基因活性，精子发生过程中基因表达的扰动与不育有关。在这里，我们使用稳态，新生和单细胞RNA测序策略来全面表征男性生殖细胞群体中的基因表达，剖析基因控制机制，并为治疗提供新的见解。我们发现了在精子分化的最早阶段暂停RNA聚合酶II（Pol II）的要求，以建立整个发育过程中基因活性的景观。因此，基因敲除未成熟生殖细胞中的Pol II暂停诱导因子NELF阻断了向精子细胞的分化。此外，我们发现意外的作用Pol II暂停在精子发生过程中的减数分裂的调节，与暂停Pol II的存在与双链断裂（DSB）的形成，减数分裂基因的表达和DSB修复缺乏NELF的生殖细胞中断。在精子发生过程中，基因表达动态受到严格调控，中断会导致不育。在这里，他们确定了RNA PolII暂停在精子发生中的关键作用，并表明RNA PolII暂停因子NELF的缺失导致减数分裂停滞。
Male germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double-strand break (DSB) formation, and disruption of meiotic gene expression and DSB repair in germ cells lacking NELF. Gene expression dynamics are tightly regulated during spermatogenesis, with disruptions resulting in infertility. Here they identify a critical role for RNA PolII pausing in spermatogenesis and show that loss of the RNA PolII pausing factor NELF causes meiotic arrest.
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DOI：
10.1016/j.jbc.2021.101231
发表时间：
2021-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Campbell KM;Xu Y;Patel C;Rayl JM;Zomer HD;Osuru HP;Pratt M;Pramoonjago P;Timken M;Miller LM;Ralph A;Storey KM;Peng Y;Drnevich J;Lagier-Tourenne C;Wong PC;Qiao H;Reddi PP
通讯作者：
Reddi PP
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
4.3
作者：
Cao, Maize C.;Scotter, Emma L.
通讯作者：
Scotter, Emma L.
影响因子：
11.8
作者：
Green CD;Ma Q;Manske GL;Shami AN;Zheng X;Marini S;Moritz L;Sultan C;Gurczynski SJ;Moore BB;Tallquist MD;Li JZ;Hammoud SS
通讯作者：
Hammoud SS
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.