ArticleNature2015
Dynamic m(6)A mRNA methylation directs translational control of heat shock response.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 841 papers, 1 of them a synthesis that pooled it.
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Who cites it
841 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,236 citations in OpenAlex.
- The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.Cell death & disease · 2024Pooled it
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
- Temporal gating dictates stress-induced transcript export from the nucleus.Genes & development · 2026Article
- Translated Circular RNAs in Glioblastoma: Emerging Regulators of Tumor Progression, Molecular Heterogeneity and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- Site-specific inhibition of translation initiation via 2'-O-methylation.Nucleic acids research · 2026Article
- How Epitranscriptomic Machinery Senses Environmental Cues.Advanced biology · 2026Review
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- NPoultry science · 2026Review
- Dual regulation of the unfolded protein response by IGF2BP3 during ER stress.Genes & development · 2026Article
- METTL14-dependent NExperimental & molecular medicine · 2026Article
- Single-nucleotide RNA mCell reports · 2026Article
- A-to-I mRNA editing: Why not simply incorporate inosine during mRNA synthesis?Molecular biology reports · 2026Review
- mArXiv · 2026Article
- The Role of NMedComm · 2026Review
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- Transcription Start Site Choice Regulates mGenes · 2026Article
- The impact of m6A modified cargo conveyed by exosomes on the tumor microenvironment.Discover oncology · 2026Review
- Single-base resolution atlas reveals moderate conservation and regulatory diversity of m6A modifications across mammals.Nucleic acids research · 2026Article
- FTO-mediated m6A demethylation regulates PGC-1α-dependent mitochondrial biogenesis to attenuate aluminum-induced neuronal senescence.Scientific reports · 2026Article
781 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology. In mammalian cells, the asymmetric distribution of m(6)A 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 m(6)A 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 m(6)A 'reader'. Upon heat shock stress, the nuclear YTHDF2 preserves 5'UTR methylation of stress-induced transcripts by limiting the m(6)A 'eraser' FTO from demethylation. Remarkably, the increased 5'UTR methylation in the form of m(6)A 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 m(6)A modification site in the 5'UTR enables translation initiation independent of the 5' end N(7)-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 m(6)A, but also uncovers a previously unappreciated translational control mechanism in heat shock response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.