Mettl14 is required for mouse postimplantation development by facilitating epiblast maturation

Abstract

N6-methyladenosine (mA) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific mA writer, reader, and eraser proteins. As an mA writer, the methyltransferase-like 3-methyltransferase-like 14 (METTL14)-Wilms tumor 1-associated protein complex dynamically regulates mA modification and plays important roles in diverse biologic processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation, and their effects on different biologic pathways are still limited. By using both in vivo and in vitro models, we here report that METTL14 is indispensable for postimplantation embryonic development by facilitating the conversion from naive to primed state of the epiblast. Depletion of Mettl14 leads to conspicuous embryonic growth retardation from embryonic d 6.5, mainly as a result of resistance to differentiation, which further leads to embryonic lethality early in gestation. Our data highlight the critical function of METTL14 as an mA modification regulator in orchestrating early mouse embryogenesis.-Meng, T.-G., Lu, X., Guo, L., Hou, G.-M., Ma, X.-S., Li, Q.-N., Huang, L., Fan, L.-H., Zhao, Z.-H., Ou, X.-H., OuYang, Y.-C., Schatten, H., Li, L., Wang, Z.-B., Sun, Q.-Y. Mettl14 is required for mouse postimplantation development by facilitating epiblast maturation.

YTHDF2 Regulates Maternal Transcriptome Degradation and Embryo Development in Goat

“…N6-methyladenosine is the most abundant internal mRNA modification, which is indispensable for pluripotency maintaining in embryonic stem cell and preimplantation development, as demonstrated by the loss function of METTL3/14 (Geula et al, 2015;Xia et al, 2018;Meng et al, 2019). In the present study, we showed that knockdown of YTHDF2 leads to an anomalous higher percentage of the 8-cell stage embryos and a lower percentage of the blastocyst in goat in vitro.…”

Identification of three m6A‐related mRNAs signature and risk score for the prognostication of hepatocellular carcinoma

“…METTL14 can positively regulate the primary microRNA 126 process in an m6A‐dependent manner to inhibit the metastatic potential of HCC . METTL14, as an important m6A methyltransferase, has been identified as playing an important role in many physiological functions and is also related to the occurrence and development of a variety of cancers . In addition, METTL14 has become a new target for treatment in EBV‐associated tumors …”

Functions of N6-methyladenosine and its role in cancer

“…METTL14 regulates post-implantation embryonic development via promoting the conversion from naive state to primed state of the epiblast. Loss of METTL14 impairs the priming and further differentiation competence of embryonic stem cells [57]. Moreover, the role of METTL14 in regulation of cancer stem cell has been revealed [58].…”