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.