Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation
By Ki-Jun Yoon, F. R. Ringeling, Caroline B. Vissers, Fadi Jacob, Michael J. Pokrass, Dennisse Jimenez-Cyrus, Yijing Su, Nam-Shik Kim, Yunhua Zhu, Lily Zheng and 10 more. Cell, 2017
679 citations recorded by the source corpus.
SUMMARY N6-methyladenosine (m6A), installed by the Mettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNA modification. Whether m6A regulates mammalian brain development is unknown. Here we show that m6A depletion by Mettl14 knockout in embryonic mouse brains prolongs cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages. m6A depletion by Mettl3 knockdown also leads to prolonged cell cycle and maintenance of radial glia cells. m6A-sequencing of embryonic mouse cortex reveals enrichment of mRNAs related to transcription factors, neurogenesis, cell cycle and neuronal differentiation, and m6A-tagging promotes their decay. Further analysis uncovers previously unappreciated transcriptional pre-patterning in cortical neural stem cells. m6A signaling also regulates human cortical neurogenesis in forebrain organoids. Comparison of m6A-mRNA landscapes between mouse and human cortical neurogenesis reveals enrichment of human-specific m6A-tagging of transcripts related to brain disorder risk genes. Our study identifies an epitranscriptomic mechanism in heightened transcriptional coordination during mammalian cortical neurogenesis.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f24bfa3405dd8dc9c1f63f804fe97f02ff6e9309
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
- Hongjun Song
- Guo-li Ming
- Chuan He
- Bryan T. Harada
- Phillip J Hsu
- Mikaela Behm
- Michaela Frye
- Ying Yang
Citations in the corpus
- FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export (2019, positive): “During mouse cortical development, multipotent Pax6 + RGCs and fate-restricted Tbr2 + intermediate progenitors (INPs) are largely depleted by postnatal stages (Dwyer et al., 2016; Yoon et al., 2017).”
- Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism (2018, background): “METTL14 and METTL3 participate in neurogenesis by modulating cell-cycle progression of cortical neural progenitor cells in an m(6)A-dependent manner.(40) METTL14 also plays a tumor-suppressor role in glioblastoma, and the depletion of METTL3 or METTL14 enhances growth and self-renewal of glioblastom”
- RNA modifications modulate gene expression during development (2018, positive): “Loss of Mettl14 (an essential component of the METTL3/14 methyltransferase complex) in the brain delays cortical neurogenesis and is associated with slower cell cycle progression and impaired decay of transcripts involved in lineage specification of cortical neural stem cells ( 21 ).”