NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells.
NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells.
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DOI：
10.1016/j.isci.2021.102762
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发表时间：
2021-07-23
期刊：
影响因子：
5.8
通讯作者：
O'Carroll D
中科院分区：
文献类型：
--
作者：
Codino A;Turowski T;van de Lagemaat LN;Ivanova I;Tavosanis A;Much C;Auchynnikava T;Vasiliauskaitė L;Morgan M;Rappsilber J;Allshire RC;Kranc KR;Tollervey D;O'Carroll D
精原干细胞(SSCs)在成年男性一生中维持精子发生和生育。保守的RNA结合蛋白NANOS2对SSCs的维持是必不可少的，但其作用靶点和机制尚不完全清楚。在这里，我们生成了一个完全功能的表位标记的Nanos2小鼠等位基因，并应用高度严格的cDNA交联和分析来定义NANOS2 RNA在SSC系中的占有率。NANOS2识别AUKAAWU共识基序，主要发现于已定义信使RNA(MRNAs)的3‘非翻译区。我们发现NANOS2是关键信号和代谢通路的调节者，其剂量或活性对SSC的维持至关重要。NANOS2与SSC系中CCR4-Not Deadenylase复合体的成分相互作用，因此，NANOS2结合减少了目标转录本的半衰期。综上所述，NANOS2通过调节靶mRNA的稳定性和关键的自我更新途径参与SSC的维持。NANOS2是一种3‘UTRmRNA结合蛋白，识别AUKAAWU共识CCR4-Not Deadenylase复合体是NANOS2在精原细胞中的主要相互作用NANOS2结合导致mRNA失稳NANOS2调节关键的精原信号和代谢途径生物科学；分子生物学；发育生物学；OMICS；转录组学
Spermatogonial stem cells (SSCs) sustain spermatogenesis and fertility throughout adult male life. The conserved RNA-binding protein NANOS2 is essential for the maintenance of SSCs, but its targets and mechanisms of function are not fully understood. Here, we generated a fully functional epitope-tagged Nanos2 mouse allele and applied the highly stringent cross-linking and analysis of cDNAs to define NANOS2 RNA occupancy in SSC lines. NANOS2 recognizes the AUKAAWU consensus motif, mostly found in the 3′ untranslated region of defined messenger RNAs (mRNAs). We find that NANOS2 is a regulator of key signaling and metabolic pathways whose dosage or activity are known to be critical for SSC maintenance. NANOS2 interacts with components of CCR4-NOT deadenylase complex in SSC lines, and consequently, NANOS2 binding reduces the half-lives of target transcripts. In summary, NANOS2 contributes to SSC maintenance through the regulation of target mRNA stability and key self-renewal pathways. NANOS2 is a 3′UTR mRNA binding protein and recognizes the AUKAAWU consensus CCR4-NOT deadenylase complex is the primary interactor of NANOS2 in spermatogonia NANOS2 binding results in mRNA destabilization NANOS2 regulates key spermatogonial signaling and metabolic pathways Biological sciences; Molecular biology; Developmental biology; Omics; Transcriptomics
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Hobbs RM;Seandel M;Falciatori I;Rafii S;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
5.2
作者：
Hasegawa, Kazuteru;Namekawa, Satoshi H.;Saga, Yumiko
通讯作者：
Saga, Yumiko
影响因子：
9.2
作者：
Chen, Dong;Zheng, Wei;Lin, Aiping;Uyhazi, Katherine;Zhao, Hongyu;Lin, Haifan
通讯作者：
Lin, Haifan
影响因子：
23.9
作者：
Hara, Kenshiro;Nakagawa, Toshinori;Enomoto, Hideki;Suzuki, Mikiko;Yamamoto, Masayuki;Simons, Benjamin D.;Yoshida, Shosei
通讯作者：
Yoshida, Shosei