TRNA Derived Small RNAs-Small Players with Big Roles

Overview

Journal Front Genet

Date 2022 Oct 6

PMID 36199575

Authors

Suja George

Mohammed Rafi

Maitha Aldarmaki

Mohamed ElSiddig

Mariam Al Nuaimi

Khaled M A Amiri

Affiliations

Soon will be listed here.

Abstract

In the past 2 decades, small non-coding RNAs derived from tRNA (tsRNAs or tRNA derived fragments; tRFs) have emerged as new powerful players in the field of small RNA mediated regulation of gene expression, translation, and epigenetic control. tRFs have been identified from evolutionarily divergent organisms from Archaea, the higher plants, to humans. Recent studies have confirmed their roles in cancers and other metabolic disorders in humans and experimental models. They have been implicated in biotic and abiotic stress responses in plants as well. In this review, we summarize the current knowledge on tRFs including types of tRFs, their biogenesis, and mechanisms of action. The review also highlights recent studies involving differential expression profiling of tRFs and elucidation of specific functions of individual tRFs from various species. We also discuss potential considerations while designing experiments involving tRFs identification and characterization and list the available bioinformatics tools for this purpose.

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References

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

Loher P, Telonis A, Rigoutsos I . MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data. Sci Rep. 2017; 7:41184. PMC: 5318995. DOI: 10.1038/srep41184. View

Cognat V, Pawlak G, Duchene A, Daujat M, Gigant A, Salinas T . PlantRNA, a database for tRNAs of photosynthetic eukaryotes. Nucleic Acids Res. 2012; 41(Database issue):D273-9. PMC: 3531208. DOI: 10.1093/nar/gks935. View

Mach J . Ticket to Ride: tRNA-Related Sequences and Systemic Movement of mRNAs. Plant Cell. 2016; 28(6):1231-2. PMC: 4944420. DOI: 10.1105/tpc.16.00493. View

Fang Y, Liu Y, Yan Y, Shen Y, Li Z, Li X . Differential Expression Profiles and Function Predictions for tRFs & tiRNAs in Skin Injury Induced by Ultraviolet Irradiation. Front Cell Dev Biol. 2021; 9:707572. PMC: 8383935. DOI: 10.3389/fcell.2021.707572. View

Robertus J, Ladner J, Finch J, Rhodes D, Brown R, Clark B . Structure of yeast phenylalanine tRNA at 3 A resolution. Nature. 1974; 250(467):546-51. DOI: 10.1038/250546a0. View

Winther K, Gerdes K . Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc Natl Acad Sci U S A. 2011; 108(18):7403-7. PMC: 3088637. DOI: 10.1073/pnas.1019587108. View

Peng Y, Zou J, Wang J, Zeng H, Tan W, Yoshida S . Small RNA Sequencing Reveals Transfer RNA-derived Small RNA Expression Profiles in Retinal Neovascularization. Int J Med Sci. 2020; 17(12):1713-1722. PMC: 7378657. DOI: 10.7150/ijms.46209. View

Chan P, Lowe T . tRNAscan-SE: Searching for tRNA Genes in Genomic Sequences. Methods Mol Biol. 2019; 1962:1-14. PMC: 6768409. DOI: 10.1007/978-1-4939-9173-0_1. View

10.

Sarker G, Sun W, Rosenkranz D, Pelczar P, Opitz L, Efthymiou V . Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. Proc Natl Acad Sci U S A. 2019; 116(21):10547-10556. PMC: 6534971. DOI: 10.1073/pnas.1820810116. View

11.

Salinas-Giege T, Giege R, Giege P . tRNA biology in mitochondria. Int J Mol Sci. 2015; 16(3):4518-59. PMC: 4394434. DOI: 10.3390/ijms16034518. View

12.

Ebhardt H, Tsang H, Dai D, Liu Y, Bostan B, Fahlman R . Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications. Nucleic Acids Res. 2009; 37(8):2461-70. PMC: 2677864. DOI: 10.1093/nar/gkp093. View

13.

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

14.

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

15.

Lu Z, Su K, Wang X, Zhang M, Ma S, Li H . Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma. Front Mol Biosci. 2022; 8:780621. PMC: 8722782. DOI: 10.3389/fmolb.2021.780621. View

16.

Chen L, Xu W, Liu K, Jiang Z, Han Y, Jin H . 5' Half of specific tRNAs feeds back to promote corresponding tRNA gene transcription in vertebrate embryos. Sci Adv. 2021; 7(47):eabh0494. PMC: 8604414. DOI: 10.1126/sciadv.abh0494. View

17.

Marchais A, Chevalier C, Voinnet O . Extensive profiling in reveals abundant polysome-associated 24-nt small RNAs including AGO5-dependent pseudogene-derived siRNAs. RNA. 2019; 25(9):1098-1117. PMC: 6800511. DOI: 10.1261/rna.069294.118. View

18.

Sega P, Kruszka K, Bielewicz D, Karlowski W, Nuc P, Szweykowska-Kulinska Z . Pi-starvation induced transcriptional changes in barley revealed by a comprehensive RNA-Seq and degradome analyses. BMC Genomics. 2021; 22(1):165. PMC: 7941915. DOI: 10.1186/s12864-021-07481-w. View

19.

Kumar P, Anaya J, Mudunuri S, Dutta A . Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Biol. 2014; 12:78. PMC: 4203973. DOI: 10.1186/s12915-014-0078-0. View

20.

Michaud M, Cognat V, Duchene A, Marechal-Drouard L . A global picture of tRNA genes in plant genomes. Plant J. 2011; 66(1):80-93. DOI: 10.1111/j.1365-313X.2011.04490.x. View