Laboratory of Animal and Genome Sciences Section, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Chiba, 263-8555, Japan.
Laboratory of Animal and Genome Sciences Section, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Chiba, 263-8555, Japan.
Biochem Biophys Res Commun. 2021 May 28;555:128-133. doi: 10.1016/j.bbrc.2021.03.117. Epub 2021 Apr 1.
mRNA decapping is a critical step in posttranscriptional regulation of gene expression in eukaryotes. Although Dcp1a is a well characterized and widely conserved mRNA decapping factor, little is known about its physiological function. To extend our understanding of Dcp1a function in vivo, we employed a transgenic rescue strategy to produce Dcp1a-deficient mice using the CRISPR/Cas9 system. This approach arrowed us to generate heterozygous Dcp1a mice and define the phenotype of Dcp1a-deficient embryos. We found that expression of Dcp1a protein, which is detectable in most mouse tissues, was developmentally regulated through embryonic growth, and that depletion of the Dcp1a gene resulted in embryonic lethality around embryonic day 10.5 (E10.5) concomitant with massive growth retardation and cardiac developmental defects. Moreover, the embryonic lethality was fully rescued by transgenic expression of exogenous human Dcp1a. Together, our results suggest that Dcp1a is required for embryonic growth.
mRNA 去帽是真核生物中基因表达转录后调控的一个关键步骤。虽然 Dcp1a 是一种特征明确且广泛保守的 mRNA 去帽因子，但对其生理功能知之甚少。为了进一步了解 Dcp1a 在体内的功能，我们利用 CRISPR/Cas9 系统通过转基因拯救策略产生 Dcp1a 缺陷型小鼠。这种方法使我们能够产生杂合子 Dcp1a 小鼠，并确定 Dcp1a 缺陷型胚胎的表型。我们发现，Dcp1a 蛋白的表达在大多数小鼠组织中均可检测到，其通过胚胎生长进行发育调控，并且 Dcp1a 基因的缺失导致胚胎在大约胚胎第 10.5 天（E10.5）死亡，同时伴有严重的生长迟缓和心脏发育缺陷。此外，外源性人 Dcp1a 的转基因表达完全挽救了胚胎致死性。总之，我们的研究结果表明 Dcp1a 对于胚胎生长是必需的。
