Identifying cortical specific long noncoding RNAs modified by m6A RNA methylation in mouse brains.

Proper development of the mammalian cerebral cortex relies on precise gene expression regulation. Increasing evidence shows that cortical development is regulated by both mRNAs and long noncoding RNAs (lncRNAs), which also are modified by N6-methyladenosine (m6A). Patterns of m6A-methylation in lncRNAs in the developing cortex have not been uncovered. Here we reveal differentially expressed lncRNAs and report stage-specific m6A-methylation patterns in lncRNAs expressed in mouse embryonic (E) and postnatal (P) cortices using RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation (MeRIP) sequencing. Many lncRNAs show temporal differential expression, and display genic distribution in the genome. Interestingly, we detect temporal-specific m6A-methylation with consensus m6A motif GGACU in the last exon in most lncRNAs. And m6A methylation levels of lncRNAs are positively correlated with the transcript abundance of lncRNAs that have no significantly differential expression in E- and P-stages. Furthermore, the transcript abundance has a positive correlation between the m6A genic lncRNAs and their nearest m6A methylated mRNAs. Our work reveals a fundamental expression reference of lncRNAs and their nearest mRNAs, and highlights an importance of m6A-mediated epitranscriptomic modifications in lncRNAs that are temporally expressed in the developing cortex.