RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis.
RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis.
复制标题
RNA结合蛋白ELAVL2在精原细胞增殖和凋亡的调节中发挥转录后作用
DOI：
10.1111/cpr.13098
复制
发表时间：
2021-09
影响因子：
8.5
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Yang C;Yao C;Ji Z;Zhao L;Chen H;Li P;Tian R;Zhi E;Huang Y;Han X;Hong Y;Zhou Z;Li Z
RNA结合蛋白（RBP）在调节精原干细胞（SSC）的维持和分化中发挥重要的转录后作用。我们从我们的单细胞测序数据中鉴定了一个保守的和SSC富集的RBP ELAVL 2，但其在SSC中的功能和机制尚不清楚。验证了ELAVL 2在人和小鼠睾丸发育过程中的表达。建立ELAVL 2过表达和敲低的稳定C18 - 4和TCam-2细胞系，用于增殖和凋亡分析。利用RNA免疫沉淀和测序技术鉴定ELAVL 2的靶基因，并研究ELAVL 2对靶基因的调控作用。利用免疫沉淀和质谱技术鉴定了人和小鼠睾丸中与ELAVL 2相互作用的蛋白，并通过体内和体外实验进行了验证。ELAVL 2是睾丸富集的，并且优先在人和小鼠SSC中表达。ELAVL 2在NOA患者中下调。ELAVL 2通过激活ERK和AKT通路促进C18 - 4和TCam-2细胞系的增殖并抑制其凋亡。ELAVL 2与编码SSCs增殖和存活的必需调节因子的mRNA相关，并在转录后水平促进其蛋白表达。在人和小鼠睾丸中，ELAVL 2在体内和体外与DAZL相互作用。总之，这些结果表明ELAVL 2是一种保守的富含SSC的RBP，在NOA中下调，通过促进靶蛋白表达来调节精原细胞增殖和凋亡。ELAVL 2在人SSC中富集并在NOA SSC中下调。ELAVL 2是精原细胞增殖和存活所必需的，其促进靶基因的蛋白表达。
RNA‐binding proteins (RBPs) play essential post‐transcriptional roles in regulating spermatogonial stem cells (SSCs) maintenance and differentiation. We identified a conserved and SSCs‐enriched RBP ELAVL2 from our single‐cell sequencing data, but its function and mechanism in SSCs were unclear. Expressions of ELAVL2 during human and mouse testis development were validated. Stable C18‐4 and TCam‐2 cell lines with overexpression and knockdown of ELAVL2 were established, which were applied to proliferation and apoptosis analysis. RNA immunoprecipitation and sequencing were used to identify ELAVL2 targets, and regulatory functions of ELAVL2 on target mRNAs were studied. Proteins interacting with ELAVL2 in human and mouse testes were identified using immunoprecipitation and mass spectrometric, which were validated by in vivo and in vitro experiments. ELAVL2 was testis‐enriched and preferentially expressed in human and mouse SSCs. ELAVL2 was down‐regulated in NOA patients. ELAVL2 promoted proliferation and inhibited apoptosis of C18‐4 and TCam‐2 cell lines via activating ERK and AKT pathways. ELAVL2 associated with mRNAs encoding essential regulators of SSCs proliferation and survival, and promoted their protein expression at post‐transcriptional level. ELAVL2 interacted with DAZL in vivo and in vitro in both human and mouse testes. Taken together, these results indicate that ELAVL2 is a conserved SSCs‐enriched RBP that down‐regulated in NOA, which regulates spermatogonia proliferation and apoptosis by promoting protein expression of targets. ELAVL2 is enriched in human SSCs and downregulated in NOA SSCs. ELAVL2 is essential for spermatogonia proliferation and survival, which promotes protein expression of target genes.
登录
查看更多内容
影响因子：
5.9
作者：
Chan AL;La HM;Legrand JMD;Mäkelä JA;Eichenlaub M;De Seram M;Ramialison M;Hobbs RM
通讯作者：
Hobbs RM
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：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
23.9
作者：
Guo J;Grow EJ;Yi C;Mlcochova H;Maher GJ;Lindskog C;Murphy PJ;Wike CL;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
小鼠睾丸中ID4+种系干细胞群的功能和分子特征。
影响因子：
10.5
作者：
Chan F;Oatley MJ;Kaucher AV;Yang QE;Bieberich CJ;Shashikant CS;Oatley JM
通讯作者：
Oatley JM