The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications
Open accessAbstract
Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) and Mettl14. To understand the role of m6A in development, we deleted Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displayed markedly decreased proliferation and premature differentiation, suggesting that m6A modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis. Mechanistically, we discovered a genome-wide increase in specific histone modifications in Mettl14 knockout versus control NSCs. These changes correlated with altered gene expression and observed cellular phenotypes, suggesting functional significance of altered histone modifications in knockout cells. Finally, we found that m6A regulates histone modification in part by destabilizing transcripts that encode histone-modifying enzymes. Our results suggest an essential role for m6A in development and reveal m6A-regulated histone modifications as a previously unknown mechanism of gene regulation in mammalian cells. Using a genetic approach, Wang et al. demonstrate an essential function for m6A mRNA modification in promoting neural stem cell proliferation and reveal interactions between m6A and histone modification as a novel gene regulatory mechanism.
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Cites
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Cited by
RNA modifications modulate gene expression during development
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m 6 A RNA methylation: from mechanisms to therapeutic potential
He, P. C., & He, C. (2021) · The EMBO Journal · doi:10.15252/embj.2020105977 · Cited by 786
Liu, J., Dou, X., Chen, C., Chen, C., Liu, C., Xu, M. M., Zhao, S., Shen, B., Gao, Y., Han, D., et al. (2020) · Science · doi:10.1126/science.aay6018 · Cited by 709
The interplay between m6A RNA methylation and noncoding RNA in cancer
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Single-base mapping of m 6 A by an antibody-independent method
Zhang, Z., Chen, L.-Q., Zhao, Y.-L., Yang, C.-G., Roundtree, I. A., Zhang, Z., Ren, J., Xie, W., He, C., & Luo, G.-Z. (2019) · Science Advances · doi:10.1126/sciadv.aax0250 · Cited by 398
Self-citation
Metadata
- Authors
- Wang, Y., Li, Y., Yue, M., Wang, J., Kumar, S., Wechsler-Reya, R. J., Zhang, Z., Ogawa, Y., Kellis, M., Duester, G., & Zhao, J. C.
- Venue
- Nature Neuroscience
- Published
- 2018-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 195-206
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2783571957
- Cited by
- 438
- References
- 57
- FWCI
- 14.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
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