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Genome Biol. 2018 May 31;19(1):68. doi: 10.1186/s13059-018-1435-z.

RNA m6A methylation participates in regulation of postnatal development of the mouse cerebellum.

Author information

1
Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Science, School of Basic Medicine Peking Union Medical College; Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
2
BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
3
University of Chinese Academy of Sciences, People's Republic of China, Beijing, 100049, China.
4
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
5
Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, NO-0027, Norway.
6
Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, NO-0317, Oslo, Norway.
7
Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Science, School of Basic Medicine Peking Union Medical College; Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China. niuym@ibms.pumc.edu.cn.
8
BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. songshh@big.ac.cn.
9
Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Science, School of Basic Medicine Peking Union Medical College; Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China. wmtong@ibms.pumc.edu.cn.

Abstract

BACKGROUND:

N6-methyladenosine (m6A) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved in the regulation of memory formation and mammalian cortical neurogenesis. However, while it is now established that m6A methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation.

RESULTS:

We identify widespread and dynamic RNA m6A methylation in the developing mouse cerebellum and further uncover distinct features of continuous and temporal-specific m6A methylation across the four postnatal developmental processes. Temporal-specific m6A peaks from P7 to P60 exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show spatiotemporal-specific expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in the mouse cerebellum. Ectopic expression of METTL3 mediated by lentivirus infection leads to disorganized structure of both Purkinje and glial cells. In addition, under hypobaric hypoxia exposure, Alkbh5-deletion causes abnormal cell proliferation and differentiation in the cerebellum through disturbing the balance of RNA m6A methylation in different cell fate determination genes. Notably, nuclear export of the hypermethylated RNAs is enhanced in the cerebellum of Alkbh5-deficient mice exposed to hypobaric hypoxia.

CONCLUSIONS:

Together, our findings provide strong evidence that RNA m6A methylation is controlled in a precise spatiotemporal manner and participates in the regulation of postnatal development of the mouse cerebellum.

KEYWORDS:

ALKBH5; Cerebellar development; METTL3; N6-methyladenosine; RNA methylation

PMID:
29855379
PMCID:
PMC5984455
DOI:
10.1186/s13059-018-1435-z
[Indexed for MEDLINE]
Free PMC Article

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