Region-specific RNA M 6 A Methylation Represents a New Layer of Control in the Gene Regulatory Network in the Mouse Brain

Open Biol. 2017 Sep;7(9):170166. doi: 10.1098/rsob.170166.

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.

Keywords: N6-methyladenosine; RNA methylation; epitranscriptomic mark; mouse cerebellum; mouse cerebral cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Animals
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks*
  • Male
  • Methylation
  • Mice
  • Molecular Sequence Annotation
  • Neurons / cytology
  • Neurons / metabolism
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • Synapses / metabolism

Substances

  • Fmr1 protein, mouse
  • RNA, Messenger
  • Fragile X Mental Retardation Protein
  • N(6)-methyladenosine
  • Adenosine