ArticleProceedings of the National Academy of Sciences of the United States of America2014
G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.
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Who cites it
232 citing papers in PubMed, 334 citations in OpenAlex.
- tRF-1-ArgTCG-1-1 promotes renal fibrosis by regulating β-catenin.Renal failure · 2026Article
- RNA G-quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.RNA biology · 2026Review
- Sex-specific regulation of angiogenin in Alzheimer's disease.Molecular psychiatry · 2026Article
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Combinatorial Model of Serum tsRNAs as a Diagnostic Biomarker for Non-Small Cell Lung Cancer.Molecular carcinogenesis · 2026Article
- tRNA-derived small RNAs in tumor microenvironment remodeling: From mechanistic insights to therapeutic perspectives.Oncogene · 2026Review
- tRNA-derived fragments elevated in Alzheimer's disease promote Tau aggregation.bioRxiv : the preprint server for biology · 2026Article
- Human small non-coding tRNA-derived fragments as key hallmarks of host-virus interaction in viral infections.Cell & bioscience · 2026Review
- Transfer RNA-derived small RNAs in female reproductive disorders: emerging roles and clinical implications.Journal of assisted reproduction and genetics · 2026Review
- Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.Nature communications · 2026Article
- Small RNA sequencing identifies serum tDR-1:34-Gly-GCC tiRNA levels as a biomarker for survival in amyotrophic lateral sclerosis.iScience · 2026Article
- Stress-induced breakup: tRNA-derived small RNAs in biology.Trends in cell biology · 2026Review
- Long Noncoding RNA Isoform Specificity and Chemical Modification on tRNA-Derived Fragments Leading to Divergent Functions.The American journal of pathology · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Epigenetic regulation in cancer metastasis.Discover oncology · 2026Review
- Hidden in plain sight: illuminating the tRNA landscape by sequencing.Genome biology · 2026Review
- The Liver FlukeBiomolecules · 2026Article
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- Striatal small RNA remodeling in MPTP-induced Parkinson's disease highlights coordinated downregulation of mitochondrial tsRNAs.Frontiers in aging neuroscience · 2026Article
- tRNA-derived fragments (tRFs) as key non-coding players in the tumor transcriptome of colorectal cancer: introducing a new suspect responsible for the remaining unknowns of tumor pathology.Medical oncology (Northwood, London, England) · 2025Review
172 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Angiogenin (ANG) is a stress-activated ribonuclease that promotes the survival of motor neurons. Ribonuclease inactivating point mutations are found in a subset of patients with ALS, a fatal neurodegenerative disease with no cure. We recently showed that ANG cleaves tRNA within anticodon loops to produce 5'- and 3'-fragments known as tRNA-derived, stress-induced RNAs (tiRNAs). Selected 5'-tiRNAs (e.g., tiRNA(Ala), tiRNA(Cys)) cooperate with the translational repressor Y-box binding protein 1 (YB-1) to displace the cap-binding complex eIF4F from capped mRNA, inhibit translation initiation, and induce the assembly of stress granules (SGs). Here, we show that translationally active tiRNAs assemble unique G-quadruplex (G4) structures that are required for translation inhibition. We show that tiRNA(Ala) binds the cold shock domain of YB-1 to activate these translational reprogramming events. We discovered that 5'-tiDNA(Ala) (the DNA equivalent of 5'-tiRNA(Ala)) is a stable tiRNA analog that displaces eIF4F from capped mRNA, inhibits translation initiation, and induces the assembly of SGs. The 5'-tiDNA(Ala) also assembles a G4 structure that allows it to enter motor neurons spontaneously and trigger a neuroprotective response in a YB-1-dependent manner. Remarkably, the ability of 5'-tiRNA(Ala) to induce SG assembly is inhibited by G4 structures formed by pathological GGGGCC repeats found in C9ORF72, the most common genetic cause of ALS, suggesting that functional interactions between G4 RNAs may contribute to neurodegenerative disease.
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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.