MT-TL1 explained
mitochondrially encoded tRNA leucine 1 (UUA/G) |
Hgncid: | 7490 |
Symbol: | MT-TL1 |
Altsymbols: | MTTL1 |
Entrezgene: | 4567 |
Omim: | 590050 |
Refseq: | NC_001807 |
Chromosome: | MT |
Mitochondrially encoded tRNA leucine 1 (UUA/G) also known as MT-TL1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL1 gene.[1]
Structure
The MT-TL1 gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 75 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3]
Function
MT-TL1 is a small 75 nucleotide RNA (human mitochondrial map position 3230–3304) that transfers the amino acid leucine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. Also, some studies showed that the MT-TL1 gene pathogenic variants could be attributed to the alterations of mTERF binding efficiency.[4]
Clinical significance
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
Mutations in MT-TL1 can result in multiple mitochondrial deficiencies and associated disorders. It is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).[5] MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.[6] A common mutation is A3243G. This mutation has been theorized to be associated with several other mitochondrial diseases,[7] including diabetes mellitus and deafness.[8] [9] Diabetes mellitus and deafness is characterized by diabetes combined with hearing loss, particularly of high pitches. Additional symptoms include muscle weakness (myopathy) and various problems with a patient's eyes, heart, or kidneys.[10]
Other rare point variants on MT-TL1 gene were also described: m.3271 T > C, m.3291 T > C, m.3303 C > T, m.3256 C > T, and m.3260 A>G.
Complex I deficiency
MT-TP mutations may result in complex I deficiency of the mitochondrial respiratory chain, which may cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). These signs and symptoms can appear at any time from birth to adulthood. Phenotypes of the condition include encephalopathy, epilepsy, dystonia, hypotonia, myalgia, exercise intolerance, and more. A 3302A>G mutation has been found in a patient with the deficiency.[11]
See also
External links
Further reading
- Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW . The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease . Journal of the Neurological Sciences . 325 . 1–2 . 165–9 . February 2013 . 23273904 . 3560033 . 10.1016/j.jns.2012.12.003 .
- Ballhausen D, Guerry F, Hahn D, Schaller A, Nuoffer JM, Bonafé L, Jeannet PY, Jacquemont S . Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study . Journal of Inherited Metabolic Disease . 33 Suppl 3 . S219-26 . December 2010 . 20458543 . 10.1007/s10545-010-9098-2 . 24006011 .
- Blakely EL, de Silva R, King A, Schwarzer V, Harrower T, Dawidek G, Turnbull DM, Taylor RW . LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation . European Journal of Human Genetics . 13 . 5 . 623–7 . May 2005 . 15657614 . 10.1038/sj.ejhg.5201363 . free .
- Ogle RF, Christodoulou J, Fagan E, Blok RB, Kirby DM, Seller KL, Dahl HH, Thorburn DR . Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin . The Journal of Pediatrics . 130 . 1 . 138–45 . January 1997 . 9003864 . 10.1016/S0022-3476(97)70323-8 .
- Houshmand M, Larsson NG, Oldfors A, Tulinius M, Holme E . Fatal mitochondrial myopathy, lactic acidosis, and complex I deficiency associated with a heteroplasmic A → G mutation at position 3251 in the mitochondrial tRNALeu(UUR) gne . Human Genetics . 97 . 3 . 269–73 . March 1996 . 8786060 . 10.1007/BF02185750 . 6688307 .
- Suzuki Y, Nishimaki K, Taniyama M, Muramatsu T, Atsumi Y, Matsuoka K, Ohta S . Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation . Diabetes Research and Clinical Practice . 63 . 3 . 225–9 . March 2004 . 14757294 . 10.1016/j.diabres.2003.10.024 .
- Huang CC, Chu CC, Pang CY, Wei YH . Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS syndrome . Acta Neurologica Scandinavica . 99 . 2 . 125–9 . February 1999 . 10071173 . 10.1111/j.1600-0404.1999.tb00670.x . 12099444 . free .
- Iwanaga R, Koga Y, Aramaki S, Kato S, Kato H . Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy . Acta Neuropathologica . 101 . 2 . 179–84 . February 2001 . 11271374 . 10.1007/s004010000266 . 1970758 .
- Nishigaki Y, Tadesse S, Bonilla E, Shungu D, Hersh S, Keats BJ, Berlin CI, Goldberg MF, Vockley J, DiMauro S, Hirano M . A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome . Neuromuscular Disorders . 13 . 4 . 334–40 . May 2003 . 12868503 . 10.1016/S0960-8966(02)00283-3 . 53265571 .
Notes and References
- Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG . Sequence and organization of the human mitochondrial genome . Nature . 290 . 5806 . 457–65 . April 1981 . 7219534 . 10.1038/290457a0 . 1981Natur.290..457A . 4355527 .
- Web site: MT-TI mitochondrially encoded tRNA isoleucine [Homo sapiens (human)] - Gene - NCBI ]. www.ncbi.nlm.nih.gov . en.
- Web site: tRNA / transfer RNA . Learn Science at Scitable .
- Bulduk BK, Kiliç HB, Bekircan-Kurt CE, Haliloğlu G, Erdem Özdamar S, Topaloğlu H, Kocaefe YÇ . A Novel Amplification-Refractory Mutation System-PCR Strategy to Screen MT-TL1 Pathogenic Variants in Patient Repositories . Genetic Testing and Molecular Biomarkers . 24 . 3 . 165–170 . March 2020 . 32167396 . 10.1089/gtmb.2019.0079 . 212693790 .
- Yasukawa T, Suzuki T, Ueda T, Ohta S, Watanabe K . Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes . The Journal of Biological Chemistry . 275 . 6 . 4251–7 . February 2000 . 10660592 . 10.1074/jbc.275.6.4251 . free .
- Web site: MT-TH gene . Genetics Home Reference . en.
- Finsterer J . Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation . Acta Neurologica Scandinavica . 116 . 1 . 1–14 . July 2007 . 17587249 . 10.1111/j.1600-0404.2007.00836.x . 43823627 . free .
- Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC . Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA . Lancet . 340 . 8832 . 1376–9 . December 1992 . 1360090 . 10.1016/0140-6736(92)92560-3 . 34540249 .
- Mazzaccara C, Iafusco D, Liguori R, Ferrigno M, Galderisi A, Vitale D, Simonelli F, Landolfo P, Prisco F, Masullo M, Sacchetti L . 6 . Mitochondrial diabetes in children: seek and you will find it . PLOS ONE . 7 . 4 . e34956 . 2012-04-19 . 22536343 . 3334935 . 10.1371/journal.pone.0034956 . 2012PLoSO...734956M . We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. . free .
- Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N . Novel mitochondrial DNA mutation in tRNA(Lys) (8296A→G) associated with diabetes . Biochemical and Biophysical Research Communications . 245 . 2 . 523–7 . April 1998 . 9571188 . 10.1006/bbrc.1998.8437 .
- van den Bosch BJ, de Coo IF, Hendrickx AT, Busch HF, de Jong G, Scholte HR, Smeets HJ . Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene . Neuromuscular Disorders . 14 . 10 . 683–8 . October 2004 . 15351426 . 10.1016/j.nmd.2004.06.004 . 38721676 .