Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans
Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans
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DOI：
10.1242/jcs.237990
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发表时间：
2020-03-01
影响因子：
4
通讯作者：
Keiper, Brett D.
中科院分区：
文献类型：
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作者：
Huggins, Hayden P.;Subash, Jacob S.;Keiper, Brett D.
生殖细胞使用正性和负性信使核糖核酸的翻译控制来调节基因表达，从而驱动其向配子分化。MRNA的翻译调控是由RNA结合蛋白、miRNAs和翻译起始因子介导的。我们已经发现了两种翻译起始因子eIF4E亚型(IFE-1和IFE-3)在线虫生殖系发育过程中与7-甲基鸟苷(M7G)mRNA帽结合的离散作用。IFE-3在生殖系性别决定(GSD)中发挥重要作用，它促进卵母细胞的命运，对精子发生是必不可少的。IFE-3在整个生殖系中表达，定位于生殖粒，但不同于IFE-1和PGL-1，促进卵母细胞的生长和存活。这与IFE-1在精母细胞中的强烈表达形成对比，IFE-1是存在于精母细胞和卵母细胞中P颗粒中的异构体，促进后期精子发生。每个eIF4E都由其同源的eIF4E结合蛋白(IFE-1：PGL-1和IFE-3：IFET-1)定位。IFE-3和IFET-1调节几个GSD mRNAs的翻译，但不调控IFE-1控制下的那些。不同的突变表型、体内定位和差异mRNA翻译表明，生殖系中的每个eIF4E亚型都有独立的休眠期和活动期。
Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1, IFE-3) that bind 7-methylguanosine (m7G) mRNA caps during Caenorhabditis elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline and localizes to germ granules, but is distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression in spermatocytes of IFE-1, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E-binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.