Editing Transfer RNA (section)

===tRNA-derived fragments===
tRNA-derived fragments (or tRFs) are short molecules that emerge after cleavage of the mature tRNAs or the precursor transcript.<ref name="Gebetsberger13">{{cite journal | vauthors = Gebetsberger J, Polacek N | title = Slicing tRNAs to boost functional ncRNA diversity | journal = RNA Biology | volume = 10 | issue = 12 | pages = 1798–1806 | date = December 2013 | pmid = 24351723 | pmc = 3917982 | doi = 10.4161/rna.27177 }}</ref><ref name="Shigematsu14">{{cite journal | vauthors = Shigematsu M, Honda S, Kirino Y | title = Transfer RNA as a source of small functional RNA | journal = Journal of Molecular Biology and Molecular Imaging | volume = 1 | issue = 2 | page = 8 | year = 2014 | pmid = 26389128 | pmc = 4572697 }}</ref><ref name="Sobala11">{{cite journal | vauthors = Sobala A, Hutvagner G | title = Transfer RNA-derived fragments: origins, processing, and functions | journal = Wiley Interdisciplinary Reviews: RNA | volume = 2 | issue = 6 | pages = 853–862 | year = 2011 | pmid = 21976287 | doi = 10.1002/wrna.96 | hdl = 10453/18187 | s2cid = 206554146 | url = https://opus.lib.uts.edu.au/bitstream/10453/18187/1/2011002529.pdf | hdl-access = free }}</ref><ref name="Keam15">{{cite journal | vauthors = Keam SP, Hutvagner G | title = tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression | journal = Life | volume = 5 | issue = 4 | pages = 1638–1651 | date = November 2015 | pmid = 26703738 | pmc = 4695841 | doi = 10.3390/life5041638 | bibcode = 2015Life....5.1638K | doi-access = free }}</ref> Both cytoplasmic and mitochondrial tRNAs can produce fragments.<ref name="Telonis15-dissect">{{cite journal | vauthors = Telonis AG, Loher P, Honda S, Jing Y, Palazzo J, Kirino Y, Rigoutsos I | title = Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies | journal = Oncotarget | volume = 6 | issue = 28 | pages = 24797–822 | date = July 2015 | pmid = 26325506 | pmc = 4694795 | doi = 10.18632/oncotarget.4695}}</ref> There are at least four structural types of tRFs believed to originate from mature tRNAs, including the relatively long tRNA halves and short 5'-tRFs, 3'-tRFs and i-tRFs.<ref name="Gebetsberger13" /><ref name="Telonis15-dissect" /><ref name="Kumar14">{{cite journal | vauthors = Kumar P, Anaya J, Mudunuri SB, Dutta A | title = Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets | journal = BMC Biology | volume = 12 | page = 78 | date = October 2014 | pmid = 25270025 | pmc = 4203973 | doi = 10.1186/s12915-014-0078-0 | doi-access = free }}</ref> The precursor tRNA can be cleaved to produce molecules from the 5' leader or 3' trail sequences. Cleavage enzymes include Angiogenin, Dicer, RNase Z and RNase P.<ref name="Gebetsberger13" /><ref name="Shigematsu14" /> Especially in the case of Angiogenin, the tRFs have a characteristically unusual cyclic phosphate at their 3' end and a hydroxyl group at the 5' end.<ref name="Honda15">{{cite journal | vauthors = Honda S, Loher P, Shigematsu M, Palazzo JP, Suzuki R, Imoto I, Rigoutsos I, Kirino Y | title = Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 29 | pages = E3816–E3825 | date = July 2015 | pmid = 26124144 | pmc = 4517238 | doi = 10.1073/pnas.1510077112 | bibcode = 2015PNAS..112E3816H | doi-access = free }}</ref> tRFs appear to play a role in [[RNA interference]], specifically in the suppression of retroviruses and retrotransposons that use tRNA as a primer for replication. Half-tRNAs cleaved by [[angiogenin]] are also known as tiRNAs. The biogenesis of smaller fragments, including those that function as [[piRNA]]s, are less understood.<ref name="pmid29934075">{{cite journal |last1=Schorn |first1=AJ |last2=Martienssen |first2=R |title=Tie-Break: Host and Retrotransposons Play tRNA. |journal=Trends in Cell Biology |date=October 2018 |volume=28 |issue=10 |pages=793–806 |doi=10.1016/j.tcb.2018.05.006 |pmid=29934075|pmc=6520983 }}</ref>

tRFs have multiple dependencies and roles; such as exhibiting significant changes between sexes, among races and disease status.<ref name="Telonis15-dissect" /><ref name="Telonis18">{{cite journal | vauthors = Telonis AG, Rigoutsos I | title = Race Disparities in the Contribution of miRNA Isoforms and tRNA-Derived Fragments to Triple-Negative Breast Cancer | journal = Cancer Res | volume = 78 | issue = 5 | pages = 1140–54 | date = March 2018 | pmid = 29229607 | pmc = 5935570 | doi = 10.1158/0008-5472.CAN-17-1947}}</ref><ref name="Telonis19">{{cite journal | vauthors = Telonis AG, Loher P, Magee R, Pliatsika V, Londin E, Kirino Y, Rigoutsos I | title = tRNA Fragments Show Intertwining with mRNAs of Specific Repeat Content and Have Links to Disparities | journal = Cancer Res | volume = 79 | issue = 12 | pages = 3034–49 | date = Jun 2019 | pmid = 30996049 | pmc = 6571059 | doi = 10.1158/0008-5472.CAN-19-0789}}</ref> Functionally, they can be loaded on Ago and act through RNAi pathways,<ref name="Sobala11" /><ref name="Kumar14" /><ref name="Shigematsu15">{{cite journal | vauthors = Shigematsu M, Kirino Y | title = tRNA-Derived Short Non-coding RNA as Interacting Partners of Argonaute Proteins | journal = Gene Regulation and Systems Biology | volume = 9 | pages = 27–33 | year = 2015 | pmid = 26401098 | pmc = 4567038 | doi = 10.4137/GRSB.S29411 }}</ref> participate in the formation of stress granules,<ref name="Emara10">{{cite journal | vauthors = Emara MM, Ivanov P, Hickman T, Dawra N, Tisdale S, Kedersha N, Hu GF, Anderson P | title = Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly | journal = The Journal of Biological Chemistry | volume = 285 | issue = 14 | pages = 10959–10968 | date = April 2010 | pmid = 20129916 | pmc = 2856301 | doi = 10.1074/jbc.M109.077560 | doi-access = free }}</ref> displace mRNAs from RNA-binding proteins<ref name="Goodarzi15">{{cite journal | vauthors = Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF | title = Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement | journal = Cell | volume = 161 | issue = 4 | pages = 790–802 | date = May 2015 | pmid = 25957686 | pmc = 4457382 | doi = 10.1016/j.cell.2015.02.053 }}</ref> or inhibit translation.<ref name="Ivanov11">{{cite journal | vauthors = Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P | title = Angiogenin-induced tRNA fragments inhibit translation initiation | journal = Molecular Cell | volume = 43 | issue = 4 | pages = 613–623 | date = August 2011 | pmid = 21855800 | pmc = 3160621 | doi = 10.1016/j.molcel.2011.06.022 }}</ref> At the system or the organismal level, the four types of tRFs have a diverse spectrum of activities. Functionally, tRFs are associated with viral infection,<ref name="Selitsky15">{{cite journal | vauthors = Selitsky SR, Baran-Gale J, Honda M, Yamane D, Masaki T, Fannin EE, Guerra B, Shirasaki T, Shimakami T, Kaneko S, Lanford RE, Lemon SM, Sethupathy P | title = Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C | journal = Scientific Reports | volume = 5 | page = 7675 | date = January 2015 | pmid = 25567797 | pmc = 4286764 | doi = 10.1038/srep07675 | bibcode = 2015NatSR...5.7675S }}</ref> cancer,<ref name="Kumar14" /> cell proliferation <ref name="Honda15" /> and also with epigenetic transgenerational regulation of metabolism.<ref name="Sharma16">{{cite journal | vauthors = Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW, Sun F, Song L, Carone BR, Ricci EP, Li XZ, Fauquier L, Moore MJ, Sullivan R, Mello CC, Garber M, Rando OJ | title = Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals | journal = Science | volume = 351 | issue = 6271 | pages = 391–396 | date = January 2016 | pmid = 26721685 | pmc = 4888079 | doi = 10.1126/science.aad6780 | bibcode = 2016Sci...351..391S }}</ref>

tRFs are not restricted to humans and have been shown to exist in multiple organisms.<ref name="Kumar14" /><ref name="Casas15">{{cite journal | vauthors = Casas E, Cai G, Neill JD | title = Characterization of circulating transfer RNA-derived RNA fragments in cattle | journal = Frontiers in Genetics | volume = 6 | page = 271 | year = 2015 | pmid = 26379699 | pmc = 4547532 | doi = 10.3389/fgene.2015.00271 | doi-access = free }}</ref><ref name="Hirose15">{{cite journal | vauthors = Hirose Y, Ikeda KT, Noro E, Hiraoka K, Tomita M, Kanai A | title = Precise mapping and dynamics of tRNA-derived fragments (tRFs) in the development of Triops cancriformis (tadpole shrimp) | journal = BMC Genetics | volume = 16 | page = 83 | date = July 2015 | pmid = 26168920 | pmc = 4501094 | doi = 10.1186/s12863-015-0245-5 | doi-access = free }}</ref><ref name="Karaiskos15">{{cite journal | vauthors = Karaiskos S, Naqvi AS, Swanson KE, Grigoriev A | title = Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets | journal = Biology Direct | volume = 10 | page = 51 | date = September 2015 | pmid = 26374501 | pmc = 4572633 | doi = 10.1186/s13062-015-0081-6 | doi-access = free }}</ref>

Two online tools are available for those wishing to learn more about tRFs: the framework for the interactive exploration of <u>mi</u>tochondrial and <u>n</u>uclear <u>t</u>RNA fragments ([https://cm.jefferson.edu/MINTbase/ MINTbase])<ref name="Pliatsika16">{{cite journal | vauthors = Pliatsika V, Loher P, Telonis AG, Rigoutsos I | title = MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments | journal = Bioinformatics | volume = 32 | issue = 16 | pages = 2481–2489 | date = August 2016 | pmid = 27153631 | pmc = 4978933 | doi = 10.1093/bioinformatics/btw194 }}</ref><ref name="Pliatsika18">{{cite journal | vauthors = Pliatsika V, Loher P, Magee R, Telonis AG, Londin E, Shigematsu M, Kirino Y, Rigoutsos I | title = MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects | journal = Nucleic Acids Research | volume = 46(D1) | pages = D152–D159 | date = January 2018 | issue = D1 | pmid = 29186503 | pmc = 5753276 | doi = 10.1093/nar/gkx1075}}</ref> and the relational database of <u>T</u>ransfer <u>R</u>NA related <u>F</u>ragments ([http://genome.bioch.virginia.edu/trfdb/ tRFdb]).<ref name="Kumar15">{{cite journal | vauthors = Kumar P, Mudunuri SB, Anaya J, Dutta A | title = tRFdb: a database for transfer RNA fragments | journal = Nucleic Acids Research | volume = 43 | issue = Database issue | pages = D141-5 | date = January 2015 | pmid = 25392422 | pmc = 4383946 | doi = 10.1093/nar/gku1138 }}</ref> MINTbase also provides a naming scheme for the naming of tRFs called [https://cm.jefferson.edu/MINTcodes/ tRF-license plates] (or MINTcodes) that is genome independent; the scheme compresses an RNA sequence into a shorter string.