Ablation of ZC3H11A causes early embryonic lethality and dysregulation of metabolic processes
ZC3H11A (zinc finger CCCH domain-containing protein 11A) is a stress-induced mRNA-binding protein required for efficient growth of nuclear-replicating viruses. The cellular functions of ZC3H11A during embryonic development are unknown. Here, we report the generation and phenotypic characterization o...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2023-06, Vol.120 (23), p.e2216799120 |
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Sprache: | eng |
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Zusammenfassung: | ZC3H11A (zinc finger CCCH domain-containing protein 11A) is a stress-induced mRNA-binding protein required for efficient growth of nuclear-replicating viruses. The cellular functions of ZC3H11A during embryonic development are unknown. Here, we report the generation and phenotypic characterization of
knockout (KO) mice. Heterozygous null
mice were born at the expected frequency without distinguishable phenotypic differences compared with wild-type mice. In contrast, homozygous null
mice were missing, indicating that
is crucial for embryonic viability and survival.
embryos were detected at the expected Mendelian ratios up to late preimplantation stage (E4.5). However, phenotypic characterization at E6.5 revealed degeneration of
embryos, indicating developmental defects around the time of implantation. Transcriptomic analyses documented a dysregulation of glycolysis and fatty acid metabolic pathways in
embryos at E4.5. Proteomic analysis indicated a tight interaction between ZC3H11A and mRNA-export proteins in embryonic stem cells. CLIP-seq analysis demonstrated that ZC3H11A binds a subset of mRNA transcripts that are critical for metabolic regulation of embryonic cells. Furthermore, embryonic stem cells with an induced deletion of
display an impaired differentiation toward epiblast-like cells and impaired mitochondrial membrane potential. Altogether, the results show that ZC3H11A is participating in export and posttranscriptional regulation of selected mRNA transcripts required to maintain metabolic processes in embryonic cells. While ZC3H11A is essential for the viability of the early mouse embryo, inactivation of
expression in adult tissues using a conditional KO did not lead to obvious phenotypic defects. |
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ISSN: | 0027-8424 1091-6490 1091-6490 |
DOI: | 10.1073/pnas.2216799120 |