Developmental Genetics, Institute of Biology, Martin Luther University Halle-Wittenberg (MLU), Weinbergweg 10, Halle (Saale) 06120, Germany.
Sci Adv. 2022 Oct 14;8(41):eabn0897. doi: 10.1126/sciadv.abn0897.
How the germ line achieves a clean transition from maternal to zygotic gene expression control is a fundamental problem in sexually reproducing organisms. Whereas several mechanisms terminate the maternal program in the soma, this combined molecular reset and handover are poorly understood for primordial germ cells (PGCs). Here, we show that GRIF-1, a TRIM32-related and presumed E3 ubiquitin ligase in , eliminates the maternal cytoplasmic poly(A) polymerase (cytoPAP) complex by targeting the germline-specific intrinsically disordered region of its enzymatic subunit, GLD-2, for proteasome-mediated degradation. Interference with cytoPAP turnover in PGCs causes frequent transgenerational sterility and, eventually, germline mortality. Hence, positively acting maternal RNA regulators are cleared via the proteasome system to avoid likely interference between maternal and zygotic gene expression programs to maintain transgenerational fertility and acquire germline immortality. This strategy is likely used in all animals that preform their immortal germ line via maternally inherited germplasm determinants.
生殖细胞如何实现从母体到合子基因表达控制的平稳过渡，是有性繁殖生物中的一个基本问题。尽管有几种机制可以在体细胞中终止母体程序，但对于原始生殖细胞（PGC），这种综合的分子重置和交接过程还知之甚少。在这里，我们表明，在 中，一种与 TRIM32 相关的假定 E3 泛素连接酶 GRIF-1，通过靶向其酶亚基 GLD-2 的种特异性无规卷曲区域，将其靶向蛋白酶体进行降解，从而消除了母体细胞质多聚（A）聚合酶（cytoPAP）复合物。在 PGC 中干扰 cytoPAP 的周转会导致频繁的跨代不育，并最终导致生殖细胞死亡。因此，通过蛋白酶体系统清除正向作用的母体 RNA 调节剂，以避免母体和合子基因表达程序之间可能的干扰，从而维持跨代生育能力并获得生殖细胞的永生性。这种策略可能被所有通过母系遗传种质决定因素来实现其不朽生殖系的动物所采用。
