Extracellular TRNAs and TRNA-derived Fragments

Overview

Journal RNA Biol

Specialty Molecular Biology

Date 2020 Feb 20

PMID 32070197

Citations 41

Authors

Juan Pablo Tosar

Alfonso Cayota

Affiliations

Soon will be listed here.

Abstract

Fragmentation of tRNAs generates a family of small RNAs collectively known as tRNA-derived fragments. These fragments vary in sequence and size but have been shown to regulate many processes involved in cell homoeostasis and adaptations to stress. Additionally, the field of extracellular RNAs (exRNAs) is rapidly growing because exRNAs are a promising source of biomarkers in liquid biopsies, and because exRNAs seem to play key roles in intercellular and interspecies communication. Herein, we review recent descriptions of tRNA-derived fragments in the extracellular space in all domains of life, both in biofluids and in cell culture. The purpose of this review is to find consensus on which tRNA-derived fragments are more prominent in each extracellular fraction (including extracellular vesicles, lipoproteins and ribonucleoprotein complexes). We highlight what is becoming clear and what is still controversial in this field, in order to stimulate future hypothesis-driven studies which could clarify the role of full-length tRNAs and tRNA-derived fragments in the extracellular space.

Citing Articles

Combinatorial Analysis of miRNAs and tRNA Fragments as Potential Biomarkers for Cancer Patients in Liquid Biopsies.

Glogovitis I, DAmbrosi S, Antunes-Ferreira M, Chiogna M, Yahubyan G, Baev V Noncoding RNA. 2025; 11(1).

PMID: 39997617 PMC: 11858735. DOI: 10.3390/ncrna11010017.

Differential expression of tRNA-derived small RNAs in Juvenile and adult sheep skin: implications for developmental and immune regulation.

Ma L, Zhao F, Zhao Z, Zhang L, Yao J, Ma Q BMC Genomics. 2025; 26(1):144.

PMID: 39953408 PMC: 11829391. DOI: 10.1186/s12864-025-11345-y.

Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington's disease.

Herrero-Lorenzo M, Perez-Perez J, Escaramis G, Martinez-Horta S, Perez-Gonzalez R, Rivas-Asensio E J Extracell Vesicles. 2024; 13(10):e12522.

PMID: 39377487 PMC: 11633361. DOI: 10.1002/jev2.12522.

The tRNA half: A strong endogenous Toll-like receptor 7 ligand with a 5'-terminal universal sequence signature.

Pawar K, Kawamura T, Kirino Y Proc Natl Acad Sci U S A. 2024; 121(19):e2319569121.

PMID: 38683985 PMC: 11087793. DOI: 10.1073/pnas.2319569121.

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application.

Zhou M, He X, Zhang J, Mei C, Zhong B, Ou C Mol Cancer. 2024; 23(1):76.

PMID: 38622694 PMC: 11020452. DOI: 10.1186/s12943-024-01992-2.

References

Bahn J, Zhang Q, Li F, Chan T, Lin X, Kim Y . The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2014; 61(1):221-30. PMC: 4332885. DOI: 10.1373/clinchem.2014.230433. View

Rodriguez-Rodrigues N, Castillo L, Landoni V, Martire-Greco D, Milillo M, Barrionuevo P . Prokaryotic RNA Associated to Bacterial Viability Induces Polymorphonuclear Neutrophil Activation. Front Cell Infect Microbiol. 2017; 7:306. PMC: 5498479. DOI: 10.3389/fcimb.2017.00306. View

Biller S, Schubotz F, Roggensack S, Thompson A, Summons R, Chisholm S . Bacterial vesicles in marine ecosystems. Science. 2014; 343(6167):183-6. DOI: 10.1126/science.1243457. View

Honda S, Kawamura T, Loher P, Morichika K, Rigoutsos I, Kirino Y . The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells. Nucleic Acids Res. 2017; 45(15):9108-9120. PMC: 5587776. DOI: 10.1093/nar/gkx537. View

Fu H, Feng J, Liu Q, Sun F, Tie Y, Zhu J . Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett. 2008; 583(2):437-42. DOI: 10.1016/j.febslet.2008.12.043. View

Nientiedt M, Deng M, Schmidt D, Perner S, Muller S, Ellinger J . Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma. Sci Rep. 2016; 6:37158. PMC: 5121638. DOI: 10.1038/srep37158. View

Santangelo L, Giurato G, Cicchini C, Montaldo C, Mancone C, Tarallo R . The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting. Cell Rep. 2016; 17(3):799-808. DOI: 10.1016/j.celrep.2016.09.031. View

Baldrich P, Rutter B, Karimi H, Podicheti R, Meyers B, Innes R . Plant Extracellular Vesicles Contain Diverse Small RNA Species and Are Enriched in 10- to 17-Nucleotide "Tiny" RNAs. Plant Cell. 2019; 31(2):315-324. PMC: 6447009. DOI: 10.1105/tpc.18.00872. View

Goodarzi H, Liu X, Nguyen H, Zhang S, Fish L, Tavazoie S . Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell. 2015; 161(4):790-802. PMC: 4457382. DOI: 10.1016/j.cell.2015.02.053. View

10.

Dhahbi J, Spindler S, Atamna H, Yamakawa A, Boffelli D, Mote P . 5' tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genomics. 2013; 14:298. PMC: 3654920. DOI: 10.1186/1471-2164-14-298. View

11.

Wilusz J . Controlling translation via modulation of tRNA levels. Wiley Interdiscip Rev RNA. 2015; 6(4):453-70. PMC: 4478206. DOI: 10.1002/wrna.1287. View

12.

Buck A, Coakley G, Simbari F, McSorley H, Quintana J, Le Bihan T . Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun. 2014; 5:5488. PMC: 4263141. DOI: 10.1038/ncomms6488. View

13.

Fromm B, Kang W, Rovira C, Cayota A, Witwer K, Friedlander M . Plant microRNAs in human sera are likely contaminants. J Nutr Biochem. 2018; 65:139-140. DOI: 10.1016/j.jnutbio.2018.07.019. View

14.

Zheng G, Qin Y, Clark W, Dai Q, Yi C, He C . Efficient and quantitative high-throughput tRNA sequencing. Nat Methods. 2015; 12(9):835-837. PMC: 4624326. DOI: 10.1038/nmeth.3478. View

15.

Nolte-t Hoen E, Buermans H, Waasdorp M, Stoorvogel W, Wauben M, t Hoen P . Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 2012; 40(18):9272-85. PMC: 3467056. DOI: 10.1093/nar/gks658. View

16.

Molnar A, Melnyk C, Bassett A, Hardcastle T, Dunn R, Baulcombe D . Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells. Science. 2010; 328(5980):872-5. DOI: 10.1126/science.1187959. View

17.

Su Z, Kuscu C, Malik A, Shibata E, Dutta A . Angiogenin generates specific stress-induced tRNA halves and is not involved in tRF-3-mediated gene silencing. J Biol Chem. 2019; 294(45):16930-16941. PMC: 6851321. DOI: 10.1074/jbc.RA119.009272. View

18.

Cozen A, Quartley E, Holmes A, Hrabeta-Robinson E, Phizicky E, Lowe T . ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat Methods. 2015; 12(9):879-84. PMC: 4553111. DOI: 10.1038/nmeth.3508. View

19.

Wilusz J, Keene J . Autoantibodies specific for U1 RNA and initiator methionine tRNA. J Biol Chem. 1986; 261(12):5467-72. View

20.

Resch U, Tsatsaronis J, Le Rhun A, Stubiger G, Rohde M, Kasvandik S . A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus. mBio. 2016; 7(6). PMC: 5090034. DOI: 10.1128/mBio.00207-16. View