Department of Veterinary and Animal Sciences, University of Massachusetts- Amherst, Amherst, MA, 01002, USA.
Department of Veterinary and Animal Sciences, University of Massachusetts- Amherst, Amherst, MA, 01002, USA.
Gene Expr Patterns. 2024 Mar;51:119346. doi: 10.1016/j.gep.2023.119346. Epub 2023 Nov 7.
Exosome Complex Components 1 and 2 (EXOSC1 and 2) are two proteins in the RNA Exosome complex whose main function is 5' → 3' RNA degradation and processing. The RNA exosome complex is comprised of nine subunits that form two separate components: the S1/KH cap and the PH-core. EXOSC1 and 2 are both part of the S1/KH cap and are involved in binding nascent RNA. As part of a systemic characterization of early lethal alleles produced by the Knockout Mouse Project, we have examined Exosc1 and Exosc2 homozygous null (mutant) embryos to determine developmental and molecular phenotypes of embryos lacking their functions. Our studies reveal that Exosc1 null embryos implant and form an egg cylinder but are developmentally delayed and fail to initiate gastrulation by embryonic day 7.5. In contrast, Exosc2 null embryos are lethal during peri-implantation stages, and while they do form a morphologically normal blastocyst at E3.5, they cannot be recovered at post-implantation stages. We show the absence of stage-specific developmental and altered lineage-specification in both Exosc1 and Exosc2 mutant embryos and conclude that these genes are essential for the successful progression through early mammalian development.
外泌体复合物成分 1 和 2（EXOSC1 和 2）是 RNA 外泌体复合物中的两种蛋白质，其主要功能是 5'→3'RNA 降解和加工。RNA 外泌体复合物由九个亚基组成，形成两个独立的组件：S1/KH 帽和 PH 核心。EXOSC1 和 2 都是 S1/KH 帽的一部分，参与结合新生 RNA。作为 Knockout Mouse Project 产生的早期致死等位基因的系统特征分析的一部分，我们检查了 Exosc1 和 Exosc2 纯合缺失（突变）胚胎，以确定缺乏这些功能的胚胎的发育和分子表型。我们的研究表明，Exosc1 缺失胚胎着床并形成卵圆柱，但发育延迟，无法在胚胎第 7.5 天启动原肠胚形成。相比之下，Exosc2 缺失胚胎在植入前阶段致死，虽然它们在 E3.5 时形成形态正常的囊胚，但不能在植入后阶段恢复。我们显示了 Exosc1 和 Exosc2 突变胚胎中缺乏阶段特异性发育和改变的谱系特异性，并得出结论，这些基因对于哺乳动物早期发育的成功进展是必不可少的。
