An essential role for Cmtr2 in mammalian embryonic development [RNA-Seq]

CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. It catalyzes 2'-O-ribose methylation of the second transcribed nucleotide of mRNAs, potentially serving to mark RNAs as “self” to evade the cellular innate immune response. Here we analyze the consequences of Cmtr2 deficiency in mice. We discover that constitutive deletion of Cmtr2 results in mouse embryos that die during mid-gestation, exhibiting defects in embryo size, placental malformation and yolk sac vascularization. Endothelial cell deletion of Cmtr2 in mice results in vascular and hematopoietic defects, and perinatal lethality. Detailed characterization of the constitutive Cmtr2 KO phenotype shows an activation of the p53 pathway and decreased proliferation, but no evidence of interferon pathway activation. In summary, our study reveals the essential roles of Cmtr2 in mammalian cells beyond its immunoregulatory function. Overall design: To examine the impact on gene expression in the Cmtr2 constitutive knockout embryos, we analyzed RNA sequences from E8.5 embryos that appeared morphologically similar to the wild-type littermate controls. We also sequenced embryos and yolk sacs isolated 1 day later at E9.5 where the Cmtr2-/- embryos are smaller than the littermate controls. E8.5 group contains samples from two different litters; E9.5 embryo and yolk sac groups contain samples from four different litters.