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

BackgroundN6-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.ResultsWe 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.ConclusionsTogether, 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.

• Publication year

  2018

• Venue

  Genome Biology

• Publication date

  2018-05-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13059-018-1435-zPMID 29855379PMCID 5984455
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Nuclear export of hypermethylated RNAs is enhanced in the cerebellum of Alkbh5-deficient mice exposed to hypobaric hypoxia.

  Confidence 0.91

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• Alkbh5-deletion under hypobaric hypoxia exposure causes abnormal cell proliferation and differentiation in the cerebellum by disturbing the balance of RNA m6A methylation in cell fate determination genes.

  Confidence 0.92

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• Ectopic expression of METTL3 mediated by lentivirus infection leads to disorganized structure of both Purkinje and glial cells in the cerebellum.

  Confidence 0.93

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• Widespread and dynamic RNA m6A methylation occurs in the developing mouse cerebellum with distinct continuous and temporal-specific features across four postnatal developmental stages.

  Confidence 0.92

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review

• alkbh5

  enzyme, protein

  An m6A eraser enzyme that removes m6A modifications from RNA and whose deletion disrupts methylation balance in the cerebellum.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• hypobaric hypoxia

  experimental condition

  An experimental condition of reduced atmospheric oxygen pressure used to probe m6A-related regulatory mechanisms in the cerebellum.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• m6a methylation

  epigenetic modification, molecular process

  An epitranscriptomic RNA modification (N6-methyladenosine) found at high abundance in the brain that regulates RNA fate and function.

  Aliases: N6-methyladenosine, m6A

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• mettl3

  enzyme, protein

  An m6A writer enzyme that deposits m6A modifications on RNA transcripts and shows spatiotemporal-specific expression in the cerebellum.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• mouse cerebellum

  anatomical structure

  The brain region studied for dynamic RNA m6A methylation changes during postnatal development.

  Aliases: cerebellum

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• postnatal development

  biological process

  The developmental period after birth (P7 to P60) during which dynamic and temporal-specific m6A methylation patterns were characterized in the cerebellum.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• purkinje cells

  cell type

  A type of large cerebellar neuron whose structural organization is disrupted by ectopic METTL3 expression.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review

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