Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer
Abstract
:1. Epitranscriptomic Transfer RNA Regulation
2. Disease Related Transfer RNA Modifications
3. Elongator Dependent Transfer RNA Modifications
4. U34 Modifications and Neurodegeneration
5. A Role of Protein Aggregation in Neurodegeneration
6. U34 Modification in Cancer
7. Phosphoregulation of Elongator Involving Kti12 and Kti14/Hrr25
8. Elongator Regulation via Kti11/Dph3 and Kti13
9. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Disease | Genes | Modification |
---|---|---|
Familial dysautonomia 1 [21,22,23] | IKBKAP | mcm5(s2)U34, ncm5U34, ncm5Um34 |
Intellectual disability 1 [24,25] | ELP2 | mcm5(s2)U34, ncm5U34, ncm5Um34 |
Amyotrophic lateral sclerosis 1 [26,27] | ELP3 | mcm5(s2)U34, ncm5U34, ncm5Um34 |
Breast-, bladder-, colorectal-, cervix- and testicular cancer1 [28] | hTRM9L * | mcm5(s2)U34 (? *) |
Urothelial cancer 2 [29] | ALKBH8 | mcm5(s2)U34 |
Asthma 1 [30] | IKBKAP | mcm5(s2)U34, ncm5U34, ncm5Um34 |
Melanoma 2,3 [31,32] | ELP1, 3, 5, 6, CTU1/2 | mcm5(s2)U34, ncm5U34, ncm5Um34 |
Invasive breast cancer 2,3 [33] | ELP3, CTU1/2 | mcm5(s2)U34, ncm5U34, ncm5Um34 |
X-linked mental retardation 1 [34] | FTSJ1 | Cm32, Gm34, yW37, ncm5Um34 |
MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) 1 [11,35,36,37] | Mt-tRNA LeuUAA´, MTO1, GTPBP3 | τm5U34 (mito) |
MERRF (myoclonus epilepsy with ragged-red fibers) 1 [11,38] | Mt-tRNA LysUUU, MTO1, GTPBP3, MTU1 | τm5s2U34 (mito) |
Deafness associated with rRNA A1555G mutation 1 [39] | MTU1 | s2U (mito) |
Acute infantile liver failure1 [40] | MTU1 | s2u (mito) |
Neurodegeneration, Galloway-Mowat syndrome1 [41,42] | YRDC, KEOPS, OSGEPL1 | t6A37 |
MERRF-like syndrome 1 [9] | YRDC, KEOPS, OSGEPL1 | t6A37 |
Type 2 diabetes 1 [43,44] | CDKAL1 | ms2t6A37 |
Breast cancer 2 [45] | TRMT12 | wybutosine37 |
Intellectual disability 1 [46,47] | PUS3 | Ψ38/39 |
Intellectual disability 1, Microcephaly 1, aggressive behavior 1 [48] | PUS7 | Ψ13/35 |
Intellectual disability 1 [49] | NSUN2 | m5C34,48,49 |
Dubowitz-like syndrome 1 [50] | NSUN2 | m5C34,48,49 |
Noonan-like syndrome 1 [51] | NSUN2 | m5C34,48,49 |
Skin-, breast- and colorectal cancer 2,3 [52,53,54] | NSUN2 | m5C34,48,49 |
Intellectual disability 1 [55] | ADAT3 | I34 |
Encephalopathy and myoclonic epilepsy 1 [56] | TRIT1 | i6A/ms2i6A37 |
Lung- and breast cancer 1 [57,58,59] | TRIT1 | i6A/ms2i6A37 |
Intellectual disability 1 [24] | TRMT1 | m2,2G26 |
Primordial dwarfism 1 [60] | METTL1/WDR4, TRM82 | m7G46 |
PEPS 1 (Partial epilepsy with pericentral spikes) [61] | TRMT44 | Um44 |
Microcephaly 1 [62,63] | TRMT10A | m1G9 |
Intellectual disability and early onset diabetes 1 [64,65], epilepsy 1 [65] | TRMT10A | m1G9 |
Breast cancer 2 [66] | TRMT2A | m5U54 |
Mitochondrial Myopathy and Sideroblastic Anemia 1 (MLASA) [67] | PUS1 | Ψmultiple (mito) |
Yeast Gene | Human Orthologs/Synonym | Modifications |
---|---|---|
ELP1 | ELP1/IKAP | mcm5s2U; mcm5U; ncm5U; ncm5Um |
ELP2 | ELP2 | mcm5s2U; mcm5U; ncm5U; ncm5Um |
ELP3 | ELP3 | mcm5s2U; mcm5U; ncm5U; ncm5Um |
ELP4 | ELP4 | mcm5s2U; mcm5U; ncm5U; ncm5Um |
ELP5 | ELP5 | mcm5s2U; mcm5U; ncm5U; ncm5Um |
ELP6 | ELP6 | mcm5s2U; mcm5U; ncm5U; ncm5Um |
TRM9 | ALKBH8, hTRM9L * | mcm5s2U; mcm5U |
TRM112 | TRMT112 | mcm5s2U; mcm5U |
NFS1 | NFS1 | mcm5s2U |
TUM1 | TUM1 | mcm5s 2U |
URM1 | URM1 | mcm5s2U |
UBA4 | UBA4 | mcm5s2U |
NCS2 | CTU1 | mcm5s2U |
NCS6 | CTU2 | mcm5s2U |
Gene | Elongation factor 2 (EF2) Modification | xm 5U34 Modification | Species | Disease/Syndrome |
---|---|---|---|---|
DPH1 | absent | present | Human | Lung cancer [205] |
Breast cancer [206,207] | ||||
Brain tumors [208] | ||||
Ovarian cancer [209,210] | ||||
Colorectal cancer [211] | ||||
Intellectual disability and craniofacial abnormalities [212,213] | ||||
Miller-Dieker syndrome (MDS) [214] | ||||
Airway obstruction and external genital abnormalities [215] | ||||
Mouse | Embryonic lethal, cell proliferation defect, edema, polydactyly [216] Embryonic jaw shortening, cleft palate [214] | |||
Fruit fly | Failure of intestinal stem cell proliferation [217] | |||
KTI11/DPH3 | absent | absent | Chinese hamster | Reduced life span hunder [218] |
Mouse | Necrosis, apoptosis and defects in development of placenta [219] | |||
DPH4 | absent | present | Mouse | Neuronal underdevelopment, impaired growth and polydactyly [220] |
DPH5 | absent | present | Fruit fly | Intestinal stem cell defect [217] |
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Hawer, H.; Hammermeister, A.; Ravichandran, K.E.; Glatt, S.; Schaffrath, R.; Klassen, R. Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer. Genes 2019, 10, 19. https://doi.org/10.3390/genes10010019
Hawer H, Hammermeister A, Ravichandran KE, Glatt S, Schaffrath R, Klassen R. Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer. Genes. 2019; 10(1):19. https://doi.org/10.3390/genes10010019
Chicago/Turabian StyleHawer, Harmen, Alexander Hammermeister, Keerthiraju Ethiraju Ravichandran, Sebastian Glatt, Raffael Schaffrath, and Roland Klassen. 2019. "Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer" Genes 10, no. 1: 19. https://doi.org/10.3390/genes10010019
APA StyleHawer, H., Hammermeister, A., Ravichandran, K. E., Glatt, S., Schaffrath, R., & Klassen, R. (2019). Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer. Genes, 10(1), 19. https://doi.org/10.3390/genes10010019