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

被引:158
作者
Ma, Chunhui [1 ,2 ]
Chang, Mengqi [1 ,2 ]
Lv, Hongyi [3 ,4 ]
Zhang, Zhi-Wei [1 ,2 ]
Zhang, Weilong [5 ]
He, Xue [1 ,2 ]
Wu, Gaolang [1 ,2 ]
Zhao, Shunli [1 ,2 ]
Zhang, Yao [1 ,2 ]
Wang, Di [1 ,2 ]
Teng, Xufei [3 ,4 ]
Liu, Chunying [1 ,2 ]
Li, Qing [1 ,2 ]
Klungland, Arne [6 ,7 ]
Niu, Yamei [1 ,2 ]
Song, Shuhui [3 ]
Tong, Wei-Min [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Sch Basic Med, Peking Union Med Coll, Dept Pathol,Inst Basic Med Sci, Beijing 100005, Peoples R China
[2] Chinese Acad Med Sci, Neurosci Ctr, Beijing 100005, Peoples R China
[3] Chinese Acad Sci, Beijing Inst Genom, BIG Data Ctr, Beijing 100101, Peoples R China
[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[5] Chinese Acad Med Sci, Peking Union Med Coll, State Key Lab Mol Oncol, Natl Canc Ctr,Canc Inst & Hosp, Beijing 100021, Peoples R China
[6] Natl Hosp Norway, Oslo Univ Hosp, Dept Microbiol, NO-0027 Oslo, Norway
[7] Univ Oslo, Inst Basic Med Sci, Dept Mol Med, NO-0317 Oslo, Norway
来源
GENOME BIOLOGY | 2018年 / 19卷
基金
中国国家自然科学基金;
关键词
N-6-methyladenosine; RNA methylation; ALKBH5; METTL3; Cerebellar development; INTEGRATIVE GENOMICS VIEWER; LARGE GENE LISTS; MESSENGER-RNA; FAT MASS; EXPRESSION ANALYSIS; N-6-METHYLADENOSINE; TRANSCRIPTOME; REVEALS; SEQ; NEUROGENESIS;
D O I
10.1186/s13059-018-1435-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: N-6-methyladenosine (m(6)A) 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 m(6)A methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation. Results: We identify widespread and dynamic RNA m(6)A methylation in the developing mouse cerebellum and further uncover distinct features of continuous and temporal-specific m(6)A methylation across the four postnatal developmental processes. Temporal-specific m(6)A peaks from P7 to P60 exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show spatiotemporal-specific expression of m(6)A 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 m(6)A 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 m(6)A methylation is controlled in a precise spatiotemporal manner and participates in the regulation of postnatal development of the mouse cerebellum.
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页数:18
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