4.6 Article

mRNA decapping factor Dcp1a is essential for embryonic growth in mice

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出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.03.117

关键词

mRNA decapping; Dcp1a; CRISPR; Cas9; Embryo; Mouse

资金

  1. Takeda Science Foundation (Grant for Visionary Research, Japan)

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mRNA decapping is a crucial step in posttranscriptional regulation, and the deficiency of Dcp1a in mice leads to embryonic lethality around E10.5 with growth retardation and cardiac defects. However, transgenic rescue with human Dcp1a can fully rescue the embryonic lethality, indicating the essential role of Dcp1a in embryonic growth.
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 develop-mentally regulated through embryonic growth, and that depletion of the Dcp1a gene resulted in em-bryonic 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 em-bryonic growth. (c) 2021 Elsevier Inc. All rights reserved.

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