ArticleThe EMBO journal2014
Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 418 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
418 citing papers in PubMed, 1 synthesis or guideline pooled it, 620 citations in OpenAlex.
- Integrating cell-type-specific gene expression and genome-wide associations identifies risk genes for schizophrenia.Molecular psychiatry · 2026Pooled it
- tRNA‑derived RNAs in hepatic diseases: From biological functions to clinical translation (Review).International journal of molecular medicine · 2026Review
- Review
- tRNA-derived small RNAs in vascular smooth muscle cell phenotypic switching and vascular remodelling.Molecular biology reports · 2026Review
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- tRNA-derived fragments elevated in Alzheimer's disease promote Tau aggregation.bioRxiv : the preprint server for biology · 2026Article
- Review
- Substrate selectivity of the human RNA mNature · 2026Article
- Inhibition of tRNA fragments dysregulated in human mTLE exacerbates pathology and seizure activity.Acta neuropathologica · 2026Article
- tRNA methylation: functional insights and epitranscriptomic regulation.Cell communication and signaling : CCS · 2026Review
- Stress-induced breakup: tRNA-derived small RNAs in biology.Trends in cell biology · 2026Review
- 5-Methylcytidine RNA Epitranscriptomics in Women's Health and Disease: Mechanisms and Clinical Implications.Cells · 2026Review
- AMPK inhibition and elevated angiogenin are associated with tRNA fragmentation in the male germline exposed to a high-fat diet.Molecular metabolism · 2026Article
- mBiology direct · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- A tRNA-derived fragment tRF3019a promotes LUAD metastasis by stabilizing hnRNPK and enhancing MYH11 expression.Cellular & molecular biology letters · 2026Article
- tRNA synthetase activity is required for stress granule and P-body assembly.Genes & development · 2026Article
- NSUN2 mediates intestinal stem cell expansion and colorectal tumour initiation via MAPK/ERK signalling.Cell death & disease · 2026Article
- Enhancing plant antiviral responses and productivity through the elimination of mScience advances · 2026Article
358 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 4 countries.
Funding
Abstract
Mutations in the cytosine-5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities in mice and human. How post-transcriptional methylation contributes to the human disease is currently unknown. By comparing gene expression data with global cytosine-5 RNA methylomes in patient fibroblasts and NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the angiogenin-mediated endonucleolytic cleavage of transfer RNAs (tRNA) leading to an accumulation of 5' tRNA-derived small RNA fragments. Accumulation of 5' tRNA fragments in the absence of NSun2 reduces protein translation rates and activates stress pathways leading to reduced cell size and increased apoptosis of cortical, hippocampal and striatal neurons. Mechanistically, we demonstrate that angiogenin binds with higher affinity to tRNAs lacking site-specific NSun2-mediated methylation and that the presence of 5' tRNA fragments is sufficient and required to trigger cellular stress responses. Furthermore, the enhanced sensitivity of NSun2-deficient brains to oxidative stress can be rescued through inhibition of angiogenin during embryogenesis. In conclusion, failure in NSun2-mediated tRNA methylation contributes to human diseases via stress-induced RNA cleavage.
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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.