The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
Aberrant methylation of t RNA s links cellular stress to neuro‐developmental disorders
Open accessAbstract
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 tRNA s 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence
Lowe, T. M., & Eddy, S. R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.5.955 · Cited by 10,905
Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications
Krueger, F., & Andrews, S. R. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr167 · Cited by 5,297
DNA methylation landscapes: Provocative insights from epigenomics
Suzuki, M. M., & Bird, A. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2341 · Cited by 3,039
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
Castello, A., Fischer, B., Eichelbaum, K., Horos, R., Beckmann, B. M., Strein, C., Davey, N. E., Humphreys, D. T., Preiss, T., Steinmetz, L. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.031 · Cited by 2,132
Diagnostic exome sequencing in persons with severe intellectual disability
de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206524 · Cited by 1,546
Kedersha, N. L., Gupta, M., Li, W., Miller, I., & Anderson, P. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.7.1431 · Cited by 1,256
Methylation of tRNA Asp by the DNA Methyltransferase Homolog Dnmt2
Goll, M. G., Kirpekar, F., Maggert, K. A., Yoder, J. A., Hsieh, C.-L., Zhang, X., Golic, K. G., Jacobsen, S. E., & Bestor, T. H. (2006) · Science · doi:10.1126/science.1120976 · Cited by 1,190
A novel class of small RNAs: tRNA-derived RNA fragments (tRFs)
Lee, Y. S., Shibata, Y., Malhotra, A., & Dutta, A. (2009) · Genes & Development · doi:10.1101/gad.1837609 · Cited by 1,173
Cited by
RNA modifications modulate gene expression during development
Frye, M., Harada, B. T., Behm, M., & He, C. (2018) · Science · doi:10.1126/science.aau1646 · Cited by 1,249
Self-citationThe expanding world of tRNA modifications and their disease relevance
Suzuki, T. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00342-0 · Cited by 743
The RNA modification landscape in human disease
Jonkhout, N., Tran, J., Smith, M. A., Schonrock, N., Mattick, J. S., & Novoa, E. M. (2017) · RNA · doi:10.1261/rna.063503.117 · Cited by 606
Bohnsack, K. E., Höbartner, C., & Bohnsack, M. T. (2019) · Genes · doi:10.3390/genes10020102 · Cited by 517
Cozen, A. E., Quartley, E., Holmes, A. D., Hrabeta-Robinson, E., Phizicky, E. M., & Lowe, T. M. (2015) · Nature Methods · doi:10.1038/nmeth.3508 · Cited by 479
Metadata
- Authors
- Blanco, S., Dietmann, S., Flores, J. V., Hussain, S., Kutter, C., Humphreys, P., Lukk, M., Lombard, P., Treps, L., Popis, M., Kellner, S., Hölter, S. M., Garrett, L., Wurst, W., Becker, L., Klopstock, T., Fuchs, H., Gailus‐Durner, V., Hrabĕ de Angelis, M., Káradóttir, R. T., Helm, M., Ule, J., Gleeson, J. G., Odom, D. T., & Frye, M.
- Venue
- The EMBO Journal
- Published
- 2014-07-25
- Volume
- 33
- Issue
- 18
- Pages
- 2020-2039
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2076772609
- Cited by
- 620
- References
- 84
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Aberrant methylation of t RNA s links cellular stress to neuro‐developmental disorders. https://app.cochat.ai/papers/10.15252/embj.201489282
- The paper
- Blanco, S., Dietmann, S., Flores, J. V., Hussain, S., Kutter, C., Humphreys, P., Lukk, M., Lombard, P., Treps, L., Popis, M., Kellner, S., Hölter, S. M., Garrett, L., Wurst, W., Becker, L., Klopstock, T., Fuchs, H., Gailus‐Durner, V., Hrabĕ de Angelis, M., . . . Frye, M. (2014). Aberrant methylation of t RNA s links cellular stress to neuro‐developmental disorders. The EMBO Journal. https://doi.org/10.15252/embj.201489282
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
