Distinct roles of Fto and Mettl3 in controlling development of the cerebral cortex through transcriptional and translational regulations
| Autor: | Zhen Zhang, Zhiwei Zeng, Tao Sun, Jinling Tang, Trevor Lee, Kunzhao Du |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Mice 129 Strain Transcription Genetic Neurogenesis Immunology Alpha-Ketoglutarate-Dependent Dioxygenase FTO Developmental neurogenesis Gestational Age Biology Methylation Article Transcriptome 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Neural Stem Cells Conditional gene knockout Translational regulation Animals Ribosome profiling Epigenetics RNA Processing Post-Transcriptional Transcriptomics Cerebral Cortex Mice Knockout Regulation of gene expression QH573-671 Gene Expression Regulation Developmental nutritional and metabolic diseases Translation (biology) Methyltransferases Cell Biology Neural progenitors Cell biology Mice Inbred C57BL 030104 developmental biology Protein Biosynthesis biology.protein Demethylase Cytology Neuroglia 030217 neurology & neurosurgery |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 7, Pp 1-12 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Proper development of the mammalian cerebral cortex relies on precise gene expression regulation, which is controlled by genetic, epigenetic, and epitranscriptomic factors. Here we generate RNA demethylase Fto and methyltransferase Mettl3 cortical-specific conditional knockout mice, and detect severe brain defects caused by Mettl3 deletion but not Fto knockout. Transcriptomic profiles using RNA sequencing indicate that knockout of Mettl3 causes a more dramatic alteration on gene transcription than that of Fto. Interestingly, we conduct ribosome profiling sequencing, and find that knockout of Mettl3 leads to a more severe disruption of translational regulation of mRNAs than deletion of Fto and results in altered translation of crucial genes in cortical radial glial cells and intermediate progenitors. Moreover, Mettl3 deletion causes elevated translation of a significant number of mRNAs, in particular major components in m6A methylation. Our findings indicate distinct functions of Mettl3 and Fto in brain development, and uncover a profound role of Mettl3 in regulating translation of major mRNAs that control proper cortical development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink