Mitochondrial Cardiomyopathy: The Roles of mt-tRNA Mutations
Abstract
:1. Introduction
2. mt-tRNA Genes and Structure
3. mt-tRNA 5′ and 3′ End Processing
4. mt-tRNA Chemical Modification
5. tRNA Aminoacylation
6. 3′ End CCA Addition
7. Import of tRNAs into Mitochondria
8. Cardiomyopathy-Associated mt-tRNA Mutations
8.1. tRNAPhe Mutation
8.2. tRNAVal Mutations
8.3. tRNALeu(UUR) Mutations
8.4. tRNAIle Mutations
8.5. tRNATrp Mutation
8.6. tRNACys Mutation
8.7. tRNASer(UCN) Mutation
8.8. tRNALys Mutations
8.9. tRNAGly Mutation
8.10. tRNAHis Mutation
8.11. tRNALeu(CUN) Mutation
8.12. tRNAGlu Mutation
8.13. tRNAThr Mutation
9. Conclusions and Future Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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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 | / | / |
tRNA Species | Mutation | Position | Structural Location | Homoplasmy/Heteroplasmy | Aberrant tRNA Biology | Clinical Diseases | References |
---|---|---|---|---|---|---|---|
tRNAPhe | T593C | 17 | D-arm | Homoplasmy | Reduced expression of functional tRNA | Cardiomyopathy, optic neuropathy, and cognitive disability | [68] |
tRNAVal | C1628T | 27 | Anticodon stem | Heteroplasmy | Reduce the steady-state level of tRNA | Cardiomyopathy, external ophthalmoplegia, and pigmentary retinitis | [72] |
tRNAVal | G1644A | 43 | Variable region | Heteroplasmy | Reduce the steady-state level of tRNA | Cardiomyopathy, loss of balance, and progressive encephalopathy | [72] |
tRNALeu(UUR) | A3243G | 14 | D-arm | Heteroplasmy | Affect steady-state level and tRNA modification | Cardiomyopathy, MELAS-like syndrome, MERRF-like syndrome, MIDD | [73,74,75,82,83,84,85] |
tRNALeu(UUR) | T3250C | 21 | D-arm | Heteroplasmy | Affect OXPHOS functions | Cardiomyopathy, mitochondrial myopathy, and exercise intolerance | [76] |
tRNALeu(UUR) | A3260G | 31 | Anticodon stem | Heteroplasmy | Affect OXPHOS functions | Maternally inheritedmyopathy and cardiomyopathy, heart failure, MELAS-like syndrome | [77,78] |
tRNALeu(UUR) | T3271C | 39 | Anticodon stem | Homoplasmy | Disrupt conserved base pairing | Hypertrophic cardiomyopathy | [79,97] |
tRNALeu(UUR) | C3303T | 72 | Acceptor arm | Heteroplasmy | Affect CCA addition | Maternally inherited myopathy and cardiomyopathy | [80] |
tRNAIle | T4277C | 15 | D-arm | Homoplasmy | Affect tRNA steady-state level | Hypertrophic cardiomyopathy, hearing impairment | [104] |
tRNAIle | A4295G | 37 | Anticodon stem | Heteroplasmy | Affect tRNA modification | Hypertrophic cardiomyopathy, hearing impairment | [105] |
tRNAIle | A4300G | 42 | Anticodon stem | Heteroplasmy | Affect steady-state level of tRNA | Maternally inherited cardiomyopathy | [108] |
tRNAIle | A4317G | 59 | TψC loop | Homoplasmy | Affect CCA addition | Fatal infantile cardiomyopathy, deafness | [111] |
tRNAIle | 4322dupC | 64 | TψC loop | Heteroplasmy | Disrupt conserved base pairing | Idiopathic dilated cardiomyopathy | [113] |
tRNATrp | G5521A | 10 | D-arm | Homoplasmy | Disrupt conserved base pairing | Maternally inherited myopathy and cardiomyopathy | [114] |
tRNACys | A5814G | 13 | D-arm | Heteroplasmy/Homoplasmy | Disrupt conserved base pairing | Maternally inherited myopathy and cardiomyopathy | [115,116] |
tRNASer(UCN) | A7495G | 20 | D-arm | Heteroplasmy | Disrupt conserved base pairing | Developmental delay, epilepsy, and cardiomyopathy | [118] |
tRNALys | T8306C | 12 | D-arm | Heteroplasmy | Disrupt conserved base pairing | Myopathy, myoclonus, leukoencephalopathy, hearing loss, hypertrophic cardiomyopathy, and insulin resistance | [119] |
tRNALys | A8344G | 53 | TψC loop | Heteroplasmy | Defect in tRNA modification | MERRF-like syndrome, cardiomyopathy, Leigh syndrome | [123] |
tRNALys | G8363A | 72 | Acceptor arm | Heteroplasmy | Affect the 3′ end processing | MERRF-like syndrome, cardiomyopathy, and Leigh syndrome | [127,128] |
tRNAGly | T9997C | 7 | Acceptor arm | Homoplasmy | Affect the 5′ end processing | Hypertrophic cardiomyopathy | [131] |
tRNAHis | G12192A | 42 | TψC loop | Homoplasmy | Disrupt conserved base pairing | LHON, hearing loss, and cardiomyopathy | [133,134] |
tRNALeu(CUN) | T12297C | 31 | Anticodon stem | Heteroplasmy | Disrupt conserved base pairing | Dilated cardiomyopathy | [135,136] |
tRNAGlu | T14709C | 36 | Anticodon stem | Heteroplasmy | Affect OXPHOS functions | Infantile cardiomyopathy, sensorineural hearing loss, and seizures | [141] |
tRNAThr | A15924G | 37 | Anticodon stem | Homoplasmy | Disrupt conserved base pairing | Dilated cardiomyopathy | [142] |
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Ding, Y.; Gao, B.; Huang, J. Mitochondrial Cardiomyopathy: The Roles of mt-tRNA Mutations. J. Clin. Med. 2022, 11, 6431. https://doi.org/10.3390/jcm11216431
Ding Y, Gao B, Huang J. Mitochondrial Cardiomyopathy: The Roles of mt-tRNA Mutations. Journal of Clinical Medicine. 2022; 11(21):6431. https://doi.org/10.3390/jcm11216431
Chicago/Turabian StyleDing, Yu, Beibei Gao, and Jinyu Huang. 2022. "Mitochondrial Cardiomyopathy: The Roles of mt-tRNA Mutations" Journal of Clinical Medicine 11, no. 21: 6431. https://doi.org/10.3390/jcm11216431