ArticleProceedings of the National Academy of Sciences of the United States of America2023
Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 61 citations in OpenAlex.
- tRNA-derived fragments elevated in Alzheimer's disease promote Tau aggregation.bioRxiv : the preprint server for biology · 2026Article
- Biofluid-specific variations in circulating 5' transfer RNA fragments during ictal and interictal states in experimental temporal lobe epilepsy.Epilepsia · 2026Article
- Stress-induced breakup: tRNA-derived small RNAs in biology.Trends in cell biology · 2026Review
- High-Throughput Sequencing Decodes tsRNA Landscapes: Insights into Cancer Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2026Review
- Hidden in plain sight: illuminating the tRNA landscape by sequencing.Genome biology · 2026Review
- Extracellular Small RNAs in Human Milk: Molecular Profiles, Stability and Fragment-Specific Responses in Cell-Based Assays.Non-coding RNA · 2026Article
- Comparative landscape of small RNAs in tissue and liquid biopsies for liver transplant outcomes.Computational and structural biotechnology journal · 2026Article
- DIS3L2-mediated RNA surveillance and extracellular vesicle packaging prevent innate immune activation by aberrant cellular RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Optimized identification and characterization of small RNAs with PANDORA-seq.Nature protocols · 2025Review
- Pseudouridine selects RNAs for extracellular transport.bioRxiv : the preprint server for biology · 2025Article
- Review
- Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025Review
- Protein Functional Effector (pfe) Noncoding RNAS Are Identical to Fragments from Various Noncoding RNAs.International journal of molecular sciences · 2025Article
- RNase L produces tRNA-derived RNAs that contribute to translation inhibition.RNA (New York, N.Y.) · 2025Article
- Altered levels of angiogenin and tRNA-derived fragments associate with severe asthma.Scientific reports · 2025Article
- Ribonuclease activity undermines immune sensing of naked extracellular RNA.Cell genomics · 2025Article
- Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential.Genome biology · 2025Article
- Article
- Diverse plant RNAs coatProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The landscape of Arabidopsis tRNA aminoacylation.The Plant journal : for cell and molecular biology · 2024Article
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10 authors at 5 institutions in 2 countries.
Funding
Abstract
Nonvesicular extracellular RNAs (nv-exRNAs) constitute the majority of the extracellular RNAome, but little is known about their stability, function, and potential use as disease biomarkers. Herein, we measured the stability of several naked RNAs when incubated in human serum, urine, and cerebrospinal fluid (CSF). We identified extracellularly produced tRNA-derived small RNAs (tDRs) with half-lives of several hours in CSF. Contrary to widespread assumptions, these intrinsically stable small RNAs are full-length tRNAs containing broken phosphodiester bonds (i.e., nicked tRNAs). Standard molecular biology protocols, including phenol-based RNA extraction and heat, induce the artifactual denaturation of nicked tRNAs and the consequent in vitro production of tDRs. Broken bonds are roadblocks for reverse transcriptases, preventing amplification and/or sequencing of nicked tRNAs in their native state. To solve this, we performed enzymatic repair of nicked tRNAs purified under native conditions, harnessing the intrinsic activity of phage and bacterial tRNA repair systems. Enzymatic repair regenerated an RNase R-resistant tRNA-sized band in northern blot and enabled RT-PCR amplification of full-length tRNAs. We also separated nicked tRNAs from tDRs by chromatographic methods under native conditions, identifying nicked tRNAs inside stressed cells and in vesicle-depleted human biofluids. Dissociation of nicked tRNAs produces single-stranded tDRs that can be spontaneously taken up by human epithelial cells, positioning stable nv-exRNAs as potentially relevant players in intercellular communication pathways.
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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.