N6 -methyladenosine (m6 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. | Ma et al. Genome Biology 2018 19 68 https s13059-018-1435-z RESEARCH Open Access RNA m6A methylation participates in regulation of postnatal development of the mouse cerebellum Chunhui Ma1 Mengqi Chang1 Hongyi Lv2 3 Zhi-Wei Zhang1 Weilong Zhang4 Xue He1 Gaolang Wu1 Shunli Zhao1 Yao Zhang1 Di Wang1 Xufei Teng2 3 Chunying Liu1 Qing Li1 Arne Klungland5 6 Yamei Niu1 Shuhui Song2 and Wei-Min Tong1 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 .
