Kleene Kenneth C
Department of Biology, University of Massachusetts Boston, Boston, Massachusetts.
Mol Reprod Dev. 2016 Mar;83(3):190-207. doi: 10.1002/mrd.22616. Epub 2016 Mar 7.
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 (3'UTR) 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 3'UTRs 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. © 2016 Wiley Periodicals, Inc.
许多编码精子特殊细胞器构建所需蛋白质的信使核糖核酸（mRNAs），在圆形精子细胞中以翻译抑制的游离信使核糖核蛋白形式储存，以便在伸长和成熟的精子细胞中进行活跃翻译。然而，在圆形精子细胞中抑制翻译的因素一直难以捉摸。有两条证据表明，高度丰富且著名的翻译抑制因子Y盒蛋白2（YBX2）是一个关键因素：第一，在Ybx2基因敲除的小鼠圆形精子细胞中，鱼精蛋白1（Prm1）和精子线粒体富含半胱氨酸蛋白（Smcp）的信使核糖核酸会过早地募集到多核糖体上。第二，3'非翻译区（3'UTR）顺式元件中的突变消除了YBX2的结合，从而激活了转基因小鼠圆形精子细胞中Prm1和Smcp信使核糖核酸的翻译。然而，YBX2的丰度及其对可变序列的亲和力，引发了关于YBX2如何靶向特定信使核糖核酸进行抑制的问题。转基因小鼠中Prm1和Smcp信使核糖核酸的突变表明，圆形精子细胞中的强抑制需要位于其3'UTR 3'端附近的YBX2结合位点，因为将相同位点定位在上游位置产生的抑制作用可忽略不计。这种位置依赖性意味着，抑制复合物的组装是由相邻的顺式元件成核的，这些元件使YBX2能够与辅助因子进行协同相互作用。现有数据表明，在脊椎动物中，YBX2通过抑制翻译活性以及通过翻译依赖性去腺苷酸化导致转录本降解，在协调圆形精子细胞中翻译抑制的信使核糖核酸的储存方面发挥着重要作用。这些见解应有助于未来旨在揭示YBX2如何靶向圆形精子细胞中的信使核糖核酸进行抑制以及YBX2基因突变如何导致人类不育的实验。《分子生殖与发育》83: 190 - 207, 2016。© 2016威利期刊公司。
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