Bioinformatic Analysis Reveals the Distinct Role of 5′UTR-Specific m6A RNA Modification in Mice Developing Cerebral Cortices

Abstract

N6-methyladenosine (m6A) abundantly exists in the cerebral cortex and is emerging as an essential factor in cortical development and function. As the m6A-binding site appears to be dynamically methylated in different RNA regions at the temporal-specific developing stage, it is of value to distinguish the unique character of region- and temporal-specific m6A. Herein, we analyzed the status of temporal-specific m6A within RNA 5′ untranslated region (5′UTR) using m6A-methylated sequencing data and transcriptomic sequencing data from 12.5- to 13-day embryonic cerebral cortices and 14-day postnatal ones. We identified sorts of RNAs that are uniquely m6A-methylated in the 5′UTR and sorted them into specific neurological processes. Compared with 3′UTR-m6A-methylated RNAs, 5′UTR-m6A-methylated RNAs showed unique functions and mechanisms in regulating cortical development, especially through the pathway of mRNA transport and surveillance. Moreover, the 5′UTR-specific m6A was associated with neurological disorders as well. The FoxO signaling pathway was then focused by these pathogenic 5′UTR-m6A-methylated RNAs and explored to be involved in the determination of neurological disorders. Additionally, the 5′UTR-m6A modification patterns and transcriptional patterns play independent but cohesive roles in the developing cortices. Our study emphasizes the importance of 5′UTR-specific m6A in the developing cortex and provides an informative reference for future studies of 5′UTR-specific m6A in normal cortical development and neurological disorders.