Division of Biological Sciences, University of Montana, Missoula, Montana 59812.
Division of Biological Sciences, University of Montana, Missoula, Montana 59812
Genetics. 2019 Feb;211(2):665-681. doi: 10.1534/genetics.118.301617. Epub 2018 Dec 3.
Developmental transitions of germ cells are often regulated at the level of post-transcriptional control of gene expression. In the germline, stem and progenitor cells exit the proliferative phase and enter meiotic differentiation to form gametes essential for fertility. The RNA binding protein GLD-1 is a cell fate regulator that promotes meiosis and germ cell differentiation during development by binding to and repressing translation of target messenger RNAs. Here, we discovered that some GLD-1 functions are promoted by binding to DLC-1, a small protein that functions as an allosteric regulator of multisubunit protein complexes. We found that DLC-1 is required to regulate a subset of GLD-1 target messenger RNAs and that DLC-1 binding GLD-1 prevents ectopic germ cell proliferation and facilitates gametogenesis Additionally, our results reveal a new requirement for GLD-1 in the events of oogenesis leading to ovulation. DLC-1 contributes to GLD-1 function independent of its role as a light chain component of the dynein motor. Instead, we propose that DLC-1 promotes assembly of GLD-1 with other binding partners, which facilitates formation of regulatory ribonucleoprotein complexes and may direct GLD-1 target messenger RNA selectivity.
生殖细胞的发育转变通常在基因表达的转录后控制水平上受到调节。在生殖系中，干细胞和祖细胞退出增殖阶段，进入减数分裂分化，形成生殖所必需的配子。RNA 结合蛋白 GLD-1 是一种细胞命运调节剂，通过与靶信使 RNA 结合并抑制其翻译，促进发育过程中的减数分裂和生殖细胞分化。在这里，我们发现 GLD-1 的一些功能是通过与 DLC-1 结合而促进的，DLC-1 是一种作为多亚基蛋白复合物的变构调节剂的小蛋白。我们发现 DLC-1 是调节 GLD-1 靶信使 RNA 的一个亚群所必需的，并且 DLC-1 结合 GLD-1 可以防止生殖细胞的异位增殖并促进配子发生。此外，我们的结果揭示了 GLD-1 在卵母细胞发生导致排卵的事件中的新要求。DLC-1 对 GLD-1 功能的贡献与其作为动力蛋白的轻链成分的作用无关。相反，我们提出 DLC-1 促进 GLD-1 与其他结合伙伴的组装，这有助于形成调节核糖核蛋白复合物，并可能指导 GLD-1 靶信使 RNA 的选择性。
