The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Dynamic m6A mRNA methylation directs translational control of heat shock response
Open accessAbstract
The most abundant mRNA post-transcriptional modification is N6-methyladenosine (m6A), which has broad roles in RNA biology. In mammalian cells, the asymmetric distribution of m6A along mRNAs results in relatively less methylation in the 5′ untranslated region (5′UTR) compared to other regions. However, whether and how 5′UTR methylation is regulated is poorly understood. Despite the crucial role of the 5′UTR in translation initiation, very little is known about whether m6A modification influences mRNA translation. Here we show that in response to heat shock stress, certain adenosines within the 5′UTR of newly transcribed mRNAs are preferentially methylated. We find that the dynamic 5′UTR methylation is a result of stress-induced nuclear localization of YTHDF2, a well-characterized m6A ‘reader’. Upon heat shock stress, the nuclear YTHDF2 preserves 5′UTR methylation of stress-induced transcripts by limiting the m6A ‘eraser’ FTO from demethylation. Remarkably, the increased 5′UTR methylation in the form of m6A promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, we demonstrate that a single m6A modification site in the 5′UTR enables translation initiation independent of the 5′ end N7-methylguanosine cap. The elucidation of the dynamic features of 5′UTR methylation and its critical role in cap-independent translation not only expands the breadth of physiological roles of m6A, but also uncovers a previously unappreciated translational control mechanism in heat shock response.
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N6-methyladenosine-dependent regulation of messenger RNA stability
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Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
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Self-citationN6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
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ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
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N6-methyladenosine Modulates Messenger RNA Translation Efficiency
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Distinctive Properties of the 5′-Untranslated Region of Human Hsp70 mRNA
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The biogenesis, biology and characterization of circular RNAs
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Reading, writing and erasing mRNA methylation
Zaccara, S., Ries, R. J., & Jaffrey, S. R. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0168-5 · Cited by 2,597
Self-citationCirc-ZNF609 is a circular RNA that can be translated and functions in myogenesis
Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173
Nuclear m6A Reader YTHDC1 Regulates mRNA Splicing
Xiao, W., Adhikari, S., Dahal, U., Chen, Y.-S., Hao, Y.-J., Sun, B.-F., Sun, H.-Y., Li, A., Ping, X.-L., Lai, W.-Y., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.012 · Cited by 2,054
Extensive translation of circular RNAs driven by N6-methyladenosine
Yang, Y., Fan, X., Mao, M., Song, X., Wu, P., Zhang, Y., Jin, Y., Yang, Y., Chen, L.-L., Wang, Y., et al. (2017) · Cell Research · doi:10.1038/cr.2017.31 · Cited by 1,855
Metadata
- Authors
- Zhou, J., Wan, J., Gao, X., Zhang, X., Jaffrey, S. R., & Qian, S.-B.
- Venue
- Nature
- Published
- 2015-10
- Volume
- 526
- Issue
- 7574
- Pages
- 591-594
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1933156045
- Cited by
- 1,236
- References
- 6
- FWCI
- 35.89
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhou, J., Wan, J., Gao, X., Zhang, X., Jaffrey, S. R., & Qian, S.-B. (2015). Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature. https://doi.org/10.1038/nature15377
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