Region-specific RNA mA methylation represents a new layer of control in the gene regulatory network in the mouse brain.

Mengqi Chang, Hongyi Lv, Weilong Zhang, Chunhui Ma, Xue He, Shunli Zhao, Zhi-Wei Zhang, Yi-Xin Zeng, Shuhui Song, Yamei Niu, Wei-Min Tong
Author Information
  1. Mengqi Chang: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
  2. Hongyi Lv: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
  3. Weilong Zhang: State Key Lab of Molecular Oncology, National Cancer Center/Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China.
  4. Chunhui Ma: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
  5. Xue He: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
  6. Shunli Zhao: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
  7. Zhi-Wei Zhang: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
  8. Yi-Xin Zeng: State Key Lab of Molecular Oncology, National Cancer Center/Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China.
  9. Shuhui Song: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China. ORCID
  10. Yamei Niu: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China niuym@ibms.pumc.edu.cn. ORCID
  11. Wei-Min Tong: Department of Pathology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China wmtong@ibms.pumc.edu.cn. ORCID

Abstract

N-methyladenosine (mA) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high mA 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 mA 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 mA methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA mA methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain.

Keywords

References

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MeSH Term

Adenosine
Animals
Cerebellum
Cerebral Cortex
Female
Fragile X Mental Retardation Protein
Gene Expression Profiling
Gene Expression Regulation
Gene Ontology
Gene Regulatory Networks
Male
Methylation
Mice
Molecular Sequence Annotation
Neurons
Organ Specificity
RNA, Messenger
Signal Transduction
Synapses

Chemicals

Fmr1 protein, mouse
RNA, Messenger
Fragile X Mental Retardation Protein
N-methyladenosine
Adenosine

Word Cloud

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