CMTR1 regulates hippocampus-dependent memory consolidation and long-term synaptic plasticity by promoting NMDA-receptor signaling

Eukaryotic mRNA is 5'-end capped with m7 guanosine, forming the cap0 (m7GpppNpNp, N: any nucleotide). Cap methyltransferase (CMTR1) further catalyzes 2'-O-ribose methylation of the first transcribed nucleotide (N1 2'-O-Me) to produce the cap1 (m7GpppNmNp) structure in all eukaryotes except yeasts. To elucidate the molecular changes in the hippocampus caused by the deletion of CMTR1 in Emx1-lineage cells, hippocampal tissues from CMTR1-cWT and cKOEmx1 mice were processed for RNA-sequencing analysis. To explore the role of CMTR1 in learning and memory, we used conditional wildtype (cWT) and conditional knock-out (cKOEmx1) mice to isolate hippocampal tissue for bulk RNA sequencing. We then ablated CMTR1 in the forebrain region to generate, a conditional knock-out (cKOCaMK2) mouse for further study. To understand the molecular changes in the hippocampus caused by the deletion of CMTR1, we used a series of behavioral, electrophysiological, and molecular assays.