Table 1.

Integrated view of human mt-tRNA modification.

Position	Location in tRNA	Modification	Human Gene	Enzymatic Activity	Function
9	D-arm	m1A	TRMT10A	Methylation	Prevention of the Watson-Crick base pairing of A-U
9	D-arm	m1G	TRMT5	Methylation	Maintenance of the tRNA structure
10	D-arm	m2G	TRMT11	Methylation	Stabilization of overall tRNA structure
16	D-arm	m1A	TRMT10A	Methylation	Increasing the steady-state level of tRNA
20	D-arm	D	DUS2L	Hydrogen addition to U	Destabilization of the helical structure
26	D-arm	m2G	TRMT1	Methylation	Stabilization of tRNA tertiary structure
26	D-arm	m22G	TRMT1	Methylation	Prevention of the Watson-Crick base pairing of G-C
27	Anticodon stem	Ψ	PUS3	Pseudouridylation	Stabilization of tRNA helical structure
28	Anticodon stem	Ψ	PUS3	Pseudouridylation	Enhancing the functions of tRNA
31	Anticodon stem	Ψ	PUS3	Pseudouridylation	Enhancing the functions of tRNA
32	Anticodon stem	m3C	METTL6	Methylation	Increasing translational output
33	Anticodon stem	Ψ	PUS3	Pseudouridylation	Increasing the stability of tRNA
34	Anticodon stem	τm5U	MTO1, GTPBP3	Taurinomethylation	Enable precise and efficient decoding
34	Anticodon stem	cmnm5U	GTPBP3	Taurinomethylation	Regulation of tRNA local structure
34	Anticodon stem	τm5s2U	MTU1	Thiolation	Regulation of tRNA local structure
34	Anticodon stem	f5C	NSUN3, ALKBH1	Methylation, Oxidization (m5C to f5C, m5Cm to hm5Cm to f5Cm)	Regulation of tRNA local structure
34	Anticodon stem	Q	hQTRT1, QTRT1	G to Q base swapping	Inhibition of RNase-mediated degradation
35	Anticodon stem	Ψ	Unidentified	/	/
37	Anticodon stem	m1G	TRMT5	Methylation	Stabilization of codon-anticodon pairing
37	Anticodon stem	t6A	YRDC, OSGEP	Threonylcarbamoylation of A	Increasing the base-stacking interactions
37	Anticodon stem	i6A	TRIT1	Isopentenylation of A	Enable precise and efficient decoding
37	Anticodon stem	ms2i6A	TRIT1, CDK5RAP1	Isopentenylation of A, Methylthiolation of i6A	Regulation of tRNA local structure
48	TψC loop	m5C	NSUN2	Methylation	Inhibition of angiogenin-mediated tRNA cleavage
49	TψC loop	m5C	NSUN2	Methylation	Inhibition of angiogenin-mediated tRNA cleavage
50	TψC loop	m5C	Unidentified	Methylation	Inhibition of angiogenin-mediated tRNA cleavage
50	TψC loop	Ψ	Unidentified	/	/
54	TψC loop	m5U	TRMT2A	Methylation	Prevention of tRNA cleavage
55	TψC loop	Ψ	Unidentified	/	/
58	TψC loop	m1A	TRMT61B	Methylation	Increasing the binding energies of T54-m1A58
66	Acceptor arm	Ψ	Unidentified	/	/
67	Acceptor arm	Ψ	Unidentified	/	/
68	Acceptor arm	Ψ	Unidentified	/	/

Abbreviations of tRNA modifications: m¹A: 1-methyladenosine; m¹G: 1-methylguanosine; m²G: N²-methylguanosine; D: dihydrouridine; m²₂G: N²,N²-dimethylguanosine; Ψ: pseudouridine; m³C: 3-methylcytidine; τm⁵U: 5-taurinomethyluridine; cmnm⁵U: 5-carboxymethylaminomethyl; τm⁵s²U: 5-taurinomethyl-2-thiouridine; f⁵C: 5-formylcytidine; Q: queuosine; t⁶A: N⁶-threonylcarbamoyladenosine; i⁶A: N⁶-isopentenyladenosine; ms²i⁶A: 2-methylthio-N⁶-isopentenyladenosine; m⁵C: 5-methylcytidine; m⁵U: 5-methyluridine.