| Experiment Id | GSE100528 | Name | METTL3-mediated m6A modification is required for cerebellar development m6A modification and cerebellar development |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-06-16 |
| description | N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of new born cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum. The mRNA expression and m6A modification were analyzed in wildtype and Mettl3 conditional knockout (Nestin-Cre) mice using postnatal day 7 and day 14 mouse cerebellums. |
