PDF(Pubmed)
Abstract：
Sex differences are pervasive in human health and disease. One major key to sex-biased differences lies in the sex chromosomes. Although the functions of the X chromosome proteins are well appreciated, how they compare with their Y chromosome homologs remains elusive. Herein, using ensemble and single-molecule techniques, we report that the sex chromosome-encoded RNA helicases DDX3X and DDX3Y are distinct in their propensities for liquid-liquid phase separation (LLPS), dissolution, and translation repression. We demonstrate that the N-terminal intrinsically disordered region of DDX3Y more strongly promotes LLPS than the corresponding region of DDX3X and that the weaker ATPase activity of DDX3Y, compared with DDX3X, contributes to the slower disassembly dynamics of DDX3Y-positive condensates. Interestingly, DDX3Y-dependent LLPS represses mRNA translation and enhances aggregation of FUS more strongly than DDX3X-dependent LLPS. Our study provides a platform for future comparisons of sex chromosome-encoded protein homologs, providing insights into sex differences in RNA metabolism and human disease.
摘要：
性别差异在人类健康和疾病中普遍存在。性别偏见差异的一个主要关键在于性染色体。虽然X染色体蛋白的功能很受欢迎，它们如何与Y染色体同源物进行比较仍然难以捉摸。在这里，使用集成和单分子技术，我们报道，性染色体编码的RNA解旋酶DDX3X和DDX3Y在液-液相分离（LLPS）的倾向上是不同的，溶出度,翻译压抑我们证明，DDX3Y的N端内在无序区域比DDX3X的相应区域更强烈地促进LLPS，并且DDX3Y的ATPase活性较弱，与DDX3X相比，有助于DDX3Y正冷凝物的拆卸动力学较慢。有趣的是,DDX3Y依赖性LLPS比DDX3X依赖性LLPS更强烈地抑制mRNA翻译并增强FUS的聚集。我们的研究为将来比较性染色体编码的蛋白质同源物提供了平台，提供对RNA代谢和人类疾病的性别差异的见解。
