Wang Xiaoling, Chang Yanjie, Li Yanping, Zhang Xiaojing, Goodrich David W
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Mol Cell Biol. 2006 Jun;26(11):4362-7. doi: 10.1128/MCB.02163-05.
The yeast TREX complex physically couples elongating RNA polymerase II with RNA processing and nuclear RNA export factors to facilitate regulated gene expression. Hpr1p is an essential component of TREX, and loss of Hpr1p compromises transcriptional elongation, RNA export, and genome stability. Despite these defects, HPR1 is not essential for viability in yeast. A functional orthologue of Hpr1p has been identified in metazoan species and is variously known as Thoc1, Hpr1, or p84. However, the physiological functions of this protein have not been determined. Here, we describe the generation and phenotypic characterization of mice containing a null allele of the Thoc1 gene. Heterozygous null Thoc1 mice are born at the expected Mendelian frequency with no phenotype distinguishable from the wild type. In contrast, homozygous null mice are not recovered, indicating that Thoc1 is required for embryonic development. Embryonic development is arrested around the time of implantation, as blastocysts exhibit hatching and blastocyst outgrowth defects upon in vitro culture. Cells of the inner cell mass are particularly dependent on Thoc1, as these cells rapidly lose viability coincident with Thoc1 protein loss. While Hpr1p is not essential for the viability of unicellular yeasts, the orthologous Thoc1 protein is required for viability of the early mouse embryo.
酵母 TREX 复合体将延伸中的 RNA 聚合酶 II 与 RNA 加工及核 RNA 输出因子物理偶联，以促进基因表达调控。Hpr1p 是 TREX 的一个必需组分，Hpr1p 的缺失会损害转录延伸、RNA 输出及基因组稳定性。尽管存在这些缺陷，但 HPR1 对酵母的生存力并非必需。已在多细胞动物物种中鉴定出 Hpr1p 的一个功能直系同源物，它有多种名称，如 Thoc1、Hpr1 或 p84。然而，该蛋白的生理功能尚未确定。在此，我们描述了含有 Thoc1 基因无效等位基因的小鼠的产生及表型特征。杂合性 Thoc1 无效小鼠以预期的孟德尔频率出生，没有可与野生型区分的表型。相比之下，纯合性无效小鼠未被获得，这表明 Thoc1 对胚胎发育是必需的。胚胎发育在着床时左右停止，因为囊胚在体外培养时表现出孵化和囊胚生长缺陷。内细胞团的细胞尤其依赖 Thoc1，因为这些细胞在 Thoc1 蛋白缺失时会迅速丧失活力。虽然 Hpr1p 对单细胞酵母的生存力并非必需，但直系同源的 Thoc1 蛋白对早期小鼠胚胎的生存力却是必需的。
