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首页> 外文期刊>Molecular reproduction and development >Position-dependent interactions of Y-box protein 2 (YBX2) with mRNA enable mRNA storage in round spermatids by repressing mRNA translation and blocking translation-dependent mRNA decay
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Position-dependent interactions of Y-box protein 2 (YBX2) with mRNA enable mRNA storage in round spermatids by repressing mRNA translation and blocking translation-dependent mRNA decay

机译:Y框蛋白2(YBX2)与mRNA的位置依赖性相互作用通过抑制mRNA翻译并阻止翻译依赖性mRNA衰变而使mRNA在圆形精子细胞中存储

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摘要

Many mRNAs encoding proteins needed for the construction of the specialized organelles of spermatozoa are stored as translationally repressed, free messenger ribonucleoproteins in round spermatids, to be actively translated in elongating and elongated spermatids. The factors that repress translation in round spermatids, however, have been elusive. Two lines of evidence implicate the highly abundant and well-known translational repressor, Y-box protein 2 (YBX2), as a critical factor: First, protamine 1 (Prm1) and sperm-mitochondria cysteine-rich protein (Smcp) mRNAs are prematurely recruited onto polysomes in Ybx2-knockout mouse round spermatids. Second, mutations in 3 untranslated region (3UTR) cis-elements that abrogate YBX2 binding activate translation of Prm1 and Smcp mRNAs in round spermatids of transgenic mice. The abundance of YBX2 and its affinity for variable sequences, however, raise questions of how YBX2 targets specific mRNAs for repression. Mutations to the Prm1 and Smcp mRNAs in transgenic mice reveal that strong repression in round spermatids requires YBX2 binding sites located near the 3 ends of their 3UTRs as locating the same sites in upstream positions produce negligible repression. This location-dependence implies that the assembly of repressive complexes is nucleated by adjacent cis-elements that enable cooperative interactions of YBX2 with co-factors. The available data suggest that, in vertebrates, YBX2 has the important role of coordinating the storage of translationally repressed mRNAs in round spermatids by inhibiting translational activity and the degradation of transcripts via translation-dependent deadenylation. These insights should facilitiate future experiments designed to unravel how YBX2 targets mRNAs for repression in round spermatids and how mutations in the YBX2 gene cause infertility in humans. Mol. Reprod. Dev. 83: 190-207, 2016. (c) 2016 Wiley Periodicals, Inc.
机译:构建精子的特殊细胞器所需的许多编码蛋白质的mRNA,被翻译抑制,游离的信使核糖核蛋白存储在圆形的精子中,在伸长和伸长的精子中被主动翻译。但是,抑制圆形精子翻译的因素却难以捉摸。有两个证据表明高度丰富且众所周知的翻译阻遏物Y-box蛋白2(YBX2)是一个关键因素:首先,鱼精蛋白1(Prm1)和富含线粒体半胱氨酸的蛋白(Smcp)mRNA过早地存在。募集到Ybx2基因敲除小鼠圆形精子中的多核糖体上。第二,取消YBX2结合的3个非翻译区(3UTR)顺式元件中的突变激活了转基因小鼠圆形精子中Prm1和Smcp mRNA的翻译。然而,YBX2的丰富性及其对可变序列的亲和力引发了有关YBX2如何靶向特定mRNA进行抑制的问题。转基因小鼠中Prm1和Smcp mRNA的突变表明,圆形精子的强阻遏作用要求YBX2结合位点位于其3UTR的3个末端附近,因为位于上游位置的相同位点产生的抑制作用可忽略不计。这种位置依赖性意味着阻遏性复合物的组装由相邻的顺式元件成核,从而使YBX2与辅因子进行协同相互作用。现有数据表明,在脊椎动物中,YBX2具有重要作用,可通过抑制翻译活性和通过翻译依赖性腺苷酸化来降解转录本,从而在圆形精子中协调翻译抑制的mRNA的存储。这些见解应有助于未来的实验,这些实验旨在揭示YBX2如何靶向圆形精子中的mRNA进行抑制,以及YBX2基因的突变如何导致人类不育。大声笑责备。开发人员83:190-207,2016年。(c)2016 Wiley Periodicals,Inc.

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