Region-specific RNA m ⁶ A methylation represents a new layer of control in the gene regulatory network in the mouse brain

Abstract

N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m6A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m6A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m6A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain.

Changes in m6A RNA methylation contribute to heart failure progression by modulating translation

“…The quality of our data was confirmed by an unbiased motif search using the detected m6A peaks as input that identified the previously reported m6A consensus sequence RRACH ( Figure 1C). Relative quantification of m6A peaks across all transcripts showed a distribution similar as in other tissues [17][18][19] with an enrichment of m6A toward the translation end site ( Figure 1D).…”

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

“…The transcriptomic profiles of m6A are spatially regulated in different brain regions (Chang et al . ). Due to technical constraints, m6A profiling in neuronal subpopulations has yet to be established.…”

“…), and subsequently supported by a bioinformatics analysis which showed a large overlap between m6A‐modified mRNAs and FMRP‐target mRNAs (Chang et al . ). Several recognition motifs of FMRP inferred from high‐throughput cross‐linking immunoprecipitation studies include the ACUK, WGGA, GAC sequences (K=G or U, W = A or U), as well as the G‐quadruplex secondary structure (Suhl et al .…”

“…m6A is highly enriched in the mammalian brain (Meyer et al 2012;Chang et al 2017). In rodents, the global level of m6A is developmentally regulated, with expression peaking in the adult brain ( Fig.…”

“…The methylated transcripts are highly biased toward neuronal genes and functions, such as synaptic function. The transcriptomic profiles of m6A are spatially regulated in different brain regions (Chang et al 2017). Due to technical constraints, m6A profiling in neuronal subpopulations has yet to be established.…”