DDX3X and DDX3Y are redundant in protein synthesis.
DDX3X and DDX3Y are redundant in protein synthesis.
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DOI：
10.1261/rna.078926.121
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Floor SN
中科院分区：
文献类型：
--
作者：
Venkataramanan S;Gadek M;Calviello L;Wilkins K;Floor SN
DDX3是一种调节翻译的死盒RNA解旋酶，由X和Y连锁的同源基因DDX3X和DDX3Y编码。虽然DDX3X在人体组织中普遍表达，对生存能力是必不可少的，但DDX3Y是男性特有的，在身体组织中的表达水平比DDX3X低，而且变化更大。DDX3X杂合性遗传损伤介导了一种称为DDX3X综合征的发育障碍，而DDX3Y的缺失与男性不育有关。DDX3X综合征偏向女性的一种可能解释是，DDX3Y编码一种具有不同生化活性的多肽。在这项研究中，我们使用核糖体图谱和体外翻译来证明DDX3的X和Y连锁的并列基因在翻译中扮演着功能冗余的角色。我们发现，对DDX3X缺失或突变敏感的转录本可以通过与DDX3Y的互补来挽救。我们的数据表明，在人类细胞的mRNA翻译过程中，DDX3X和DDX3Y蛋白可以在功能上相互补充。DDX3Y在很大一部分中枢神经系统中不表达。这些发现表明，DDX3X相关疾病的性别偏见的基础是表达的差异，而不是平行对数依赖的蛋白质合成的差异。
DDX3 is a DEAD-box RNA helicase that regulates translation and is encoded by the X- and Y-linked paralogs DDX3X and DDX3Y. While DDX3X is ubiquitously expressed in human tissues and essential for viability, DDX3Y is male-specific and shows lower and more variable expression than DDX3X in somatic tissues. Heterozygous genetic lesions in DDX3X mediate a class of developmental disorders called DDX3X syndrome, while loss of DDX3Y is implicated in male infertility. One possible explanation for female-bias in DDX3X syndrome is that DDX3Y encodes a polypeptide with different biochemical activity. In this study, we use ribosome profiling and in vitro translation to demonstrate that the X- and Y-linked paralogs of DDX3 play functionally redundant roles in translation. We find that transcripts that are sensitive to DDX3X depletion or mutation are rescued by complementation with DDX3Y. Our data indicate that DDX3X and DDX3Y proteins can functionally complement each other in the context of mRNA translation in human cells. DDX3Y is not expressed in a large fraction of the central nervous system. These findings suggest that expression differences, not differences in paralog-dependent protein synthesis, underlie the sex-bias of DDX3X-associated diseases.
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