Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction.
Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction.
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DOI：
10.1101/gr.276578.122
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发表时间：
2022-09-27
期刊：
影响因子：
7
通讯作者：
Lesch, Bluma J.
中科院分区：
文献类型：
--
作者：
Griffin, Kimberly N.;Walters, Benjamin William;Li, Haixin;Wang, Huafeng;Biancon, Giulia;Tebaldi, Toma;Kaya, Carolyn B.;Kanyo, Jean;Lam, TuKiet T.;Cox, Andy L.;Halene, Stephanie;Chung, Jean-Ju;Lesch, Bluma J.
Argonaute 2（AGO2）是一种广泛表达的蛋白质，对mRNA翻译的调节至关重要，对动物发育至关重要。AGO2蛋白存在于细胞质和细胞核中，尽管其细胞质作用已被充分研究，但细胞核AGO2的生物学相关性尚不清楚。在这里，我们解决这个问题，在体内使用生精细胞作为模型。我们发现，AGO2瞬时结合的染色质和细胞核特异性mRNA转录的精子生产所需的数百个基因在小鼠雄性减数分裂过程中，和生殖系条件性敲除（cKO）的Ago2的编码蛋白质的原因耗尽。相应地，Ago2 cKO雄性显示异常的精子头形态和减少的精子计数，沿着后代出生后活力降低。总之，我们的数据揭示了一个意想不到的核心作用AGO2在提高哺乳动物雄性生殖过程中的发育重要基因的表达。
Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction.
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影响因子：
16
作者：
Biancon G;Joshi P;Zimmer JT;Hunck T;Gao Y;Lessard MD;Courchaine E;Barentine AES;Machyna M;Botti V;Qin A;Gbyli R;Patel A;Song Y;Kiefer L;Viero G;Neuenkirchen N;Lin H;Bewersdorf J;Simon MD;Neugebauer KM;Tebaldi T;Halene S
通讯作者：
Halene S
Argonaute在人核RNA中结合及其对替代剪接的影响。
DOI：
10.1261/rna.078707.121
发表时间：
2021-09
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Chu Y;Yokota S;Liu J;Kilikevicius A;Johnson KC;Corey DR
通讯作者：
Corey DR
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
64.8
作者：
Cernilogar, Filippo M.;Onorati, Maria Cristina;Kothe, Greg O.;Burroughs, A. Maxwell;Parsi, Krishna Mohan;Breiling, Achim;Lo Sardo, Federica;Saxena, Alka;Miyoshi, Keita;Siomi, Haruhiko;Siomi, Mikiko C.;Carninci, Piero;Gilmour, David S.;Corona, Davide F. V.;Orlando, Valerio
通讯作者：
Orlando, Valerio
影响因子：
1.5
作者：
Gallardo, Teresa;Shirley, Lane;Castrillon, Diego H.
通讯作者：
Castrillon, Diego H.