RNA m6A methylation participates in regulation of postnatal development of the mouse cerebellum.
Ma C1, Chang M1, Lv H2,3, Zhang ZW1, Zhang
W4, He X1, Wu G1, Zhao S1, Zhang Y1, Wang D1, Teng X2,3, Liu C1, Li Q1,
Klungland A5,6, Niu Y7, Song S8, Tong WM9.
Genome Biol. 2018 May 31;19(1):68.
PMID: 29855379
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.