Table 1.

Functions of various tRNA-derived RNA fragments in human diseases

Types of disease	Types of tRFs, tsRNAs, and tiRNAs	Parent tRNA	Functions of tRFs, tsRNAs and tiRNAs	References
Cancer	3′-tRF-1001	tRNA-SerTGA	promote prostate cancer cell proliferation	34
	tRF-544	tRNA-PheGAA	significantly downregulated and associated with aggressive tumor growth	5,6
	tRF-315	tRNA-LysCTT
	3′-CCA-tRF (CU1276)	tRNA-Gly	gene silencing and post-transcriptional regulation in lymphoma cell lines	29
	tRF-19	tRNA-ArgACG	differentially expressed in mammary epithelium and malignant breast tumors in response to deregulation of RUNX1	35
	tRF-29	tRNA-TyrGTA
	tRF-46	tRNA-HisGTG
	tRF-112	tRNA-SerGCT
	tRF-Glu	tRNA-GluYTC	these tRFs interact with YBX1 protein and displace multiple oncogenic transcripts, which results in their instability and finally the suppression of breast cancer	36
	tRF-Asp	tRNA-AspGTC
	tRF-Gly	tRNA-GlyTCC
	ts-4521	3′ ends of pre-tRNAs of serine and 3′ ends of pre-tRNAs of threonine	these tRFs interacts with Ago and Piwi-like proteins, which supports cancer cell proliferation in lungs	37,38
	ts-3676
	tRF AS-tDR-000064	tRNA-LeuAAG	displayed abundant differential expression in pancreatic cancer cells compared to adjacent normal tissues	39
	tRF AS-tDR-000069	tRNA-GlnCTG
	tRF AS-tDR-000102	tRNA-AlaCGC
	tRF AS-tDR-001391	tRNA-ProCGG
	tRF AS-tDR-000064	tRNA-LeuAAG	qPCR data validated their upregulation in pancreatic cancer	39
	tRF AS-tDR-000069	tRNA-GlnCTG
	tRF AS-tDR-000102	tRNA-AlaCGC
	AS-tDR-001391	tRNA-ProCGG	qPCR data validated its downregulation in pancreatic cancer	39
	5′-tRF-His	tRNA-His	inhibits the proliferation of breast cancer by regulating CKAP2	40
	tRF-Glu-CTC-003	tRNA-GluCTC	functions are not characterized; however, these can be used as a biomarker in early breast cancer detection	41
	tRF-Gly-CCC-007 tRF-Gly-CCC-008 tRF-Leu-CAA-003	tRNA-GlyCCC
	tRF-Ser-TGA-001	tRNA-LeuCAA
	tRF-Ser-TGA-002	tRNA-SerTGA
		tRNA-SerTGA
	5′-tRNA-Val-CAC-2-1 half	tRNA-ValCAC	negatively regulates G1/S transition of mitotic cell cycle	42,43
	3′-tsRNA-CAGLeu	tRNA-LeuCAG	this 3′-tsRNA interacts with mRNA of ribosomal proteins RPS28 and RPS15, which results in translation promotion and finally leads to proliferation of hepatocellular carcinoma cells	44
	tRF-3017A	tRNA-Val TAC	tRF-3017A regulates the NELL2 tumor suppressor gene and thus promotes metastasis in gastric cancer	45
Infectious disease	tRNA-GluCTC	tRNAGlu	represses the target mRNA in the cytoplasm and facilitates RSV replication	46,47
	tRF5-GlyCCC	tRNA-GlyCCC	promote RSV replication	46
	tRF5-LysCTT	tRNA-LysCTT
	tRF5-GluCTC	tRNAGlu	suppresses APOER2 mRNA and facilitates RSV replication	47
	tRFs		binds with reverse transcriptase of human T cell leukemia virus-1 and alters replication	48
	tRF-3019	tRNAPro
	tRNAThr 3′ half (this tRF is produced in human pathogenic protozoa, Trypanosoma brucei)	tRNAThr	binds with ribosome and stimulates protein biosynthesis during the stress recovery phase	49
	5′ and 3′ half of tRNAs (these tRFs are produced in human pathogenic fungus)	produced by endonucleolytic cleavage within the anticodon loop during conidiogenesis in Aspergillus fumigatus	protein synthesis is downregulated	50
	5′-tsRNAAsp	tRNAAsp	these tsRNAs interact with macrophages and support Leishmania donovani and Leishmania braziliensis to seek entry into cell cytoplasm	23
	5′-tsRNAGln	tRNAGln
	3′-tRF-AlaUGC (includes 3′-CCA)	tRNA-AlaUGC	this tRF stimulates TLRs and thus Thp1- and CTL1-mediated immune responses	51
	3′-tRF-SerTGA	tRNA-SerTGA	this 3′-tRF interacts with La/SSB proteins and resists IRES-mediated translation during HCV infection	52
Neurodegenerative diseases	5′-tiRNA-Ala and 5′-tiRNA-Cys	tRNAAla and tRNACys	these interact with YB-1 protein and induce the assembly of stress granules (SGs), which further generates a neuroprotective response	53
	5′-tiRNAAsp, tiRNAGlu, tiRNAGly, tiRNAHis, tiRNALys, tiRNAVal	tRNAAsp, tRNAGlu, tRNAGly, tRNAHis, tRNALys, tRNAVal	these 5′-tRNA halves accumulate as a result of Nsun2 and Dnmt2 methyltransferase mutation, which results in reduced translation and action of apoptotic and stress pathways; this further leads to reduced cell size of hippocampal, cortical. and striatal neurons	54
	3′- and 5′-tRNA halves	derived from different isoacceptor tRNAs such as tyrosine, leucine, and isoleucine	CLP1 protein deficiency in the case of pontocerebellar hypoplasia (PCH) results in unspliced pre-tRNA, which results in accumulation of 5′- and 3′-tRNA halves in the cells	17,55,56
Development and inheritance	5′-tRNA halves	derived from tRNA-GlyGCC, tRNA-ValCAC, tRNA-GlnCTG, tRNA-GluTTC, tRNA-LysTTT	these interact with IGF2BP1 and regulate the translation of cMyc, which further regulates cell proliferation and metabolism	42
	5′-tRFGlyGCC	tRNA-GlyGCC	this targets MERVL an endogenous retroelement, which affects placentation and finally culminates in altered development of the offspring	57
Metabolic disease	tRF-3001b	tRNA-AsnGTT	this interacts with Prkaa1 and inhibits autophagy, which stimulates NAFLD development	58
	Gly-tRFs	tRNAGly	involved in the progression of liver steatosis	59
Immunity	tRF5-AlaCGC	tRNA-AlaCGC	tRF5-AlaCGC induces IL-8 production by stimulating p65	60
	5′-tiRNA-GluCTC	tRNA-GluCTC	this tRF induces chemokine and cytokine production	47
	tRF-LysAAA	tRNA-LysAAA	involved in immunity regulation	61
	tRF-AspGAY	tRNA-AspGAY
Aging	tRF-3003a	tRNA-CysGCA	regulates OA pathogenesis by repressing the Janus kinase 3 (JAK3) pathway	62
	tiRNA-5035-GluCTC	both derived from tRNA-GluCTC	differential expression studies showed the downregulation of these tRFs in metacarpophalangeal joints of old horses	63
	tiRNA-5031-GluCTC-1
	5′-tRNA halves	derived from tRNA-AsnGTT, tRNA-IleAAT, and tRNA-AspGTC	downregulation of these tRFs was observed in rheumatoid arthritis patients, which suggests its use as a putative biomarker	64