MT-TL1

mitochondrially encoded tRNA leucine 1 (UUA/G)
mitochondrially encoded tRNA leucine 1 (UUA/G)
Identifiers
Symbol	MT-TL1
Alt. symbols	MTTL1
NCBI gene	4567
HGNC	7490
OMIM	590050
RefSeq	NC_001807
Other data
Locus	Chr. MT [1]

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.^[4]

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]

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 (April 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID 7219534. S2CID 4355527.
^ "MT-TI mitochondrially encoded tRNA isoleucine [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
^ "tRNA / transfer RNA". Learn Science at Scitable.
^ ^a ^b Bulduk BK, Kiliç HB, Bekircan-Kurt CE, Haliloğlu G, Erdem Özdamar S, Topaloğlu H, Kocaefe YÇ (March 2020). "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. doi:10.1089/gtmb.2019.0079. PMID 32167396. S2CID 212693790.
^ Yasukawa T, Suzuki T, Ueda T, Ohta S, Watanabe K (February 2000). "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. doi:10.1074/jbc.275.6.4251. PMID 10660592.
^ "MT-TH gene". Genetics Home Reference. This article incorporates text from this source, which is in the public domain.
^ Finsterer J (July 2007). "Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation". Acta Neurologica Scandinavica. 116 (1): 1–14. doi:10.1111/j.1600-0404.2007.00836.x. PMID 17587249. S2CID 43823627.
^ Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC (December 1992). "Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA". Lancet. 340 (8832): 1376–9. doi:10.1016/0140-6736(92)92560-3. PMID 1360090. S2CID 34540249.
^ Mazzaccara C, Iafusco D, Liguori R, Ferrigno M, Galderisi A, Vitale D, et al. (2012-04-19). "Mitochondrial diabetes in children: seek and you will find it". PLOS ONE. 7 (4): e34956. Bibcode:2012PLoSO...734956M. doi:10.1371/journal.pone.0034956. PMC 3334935. PMID 22536343. 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.
^ Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N (April 1998). "Novel mitochondrial DNA mutation in tRNA(Lys) (8296A→G) associated with diabetes". Biochemical and Biophysical Research Communications. 245 (2): 523–7. doi:10.1006/bbrc.1998.8437. PMID 9571188.
^ van den Bosch BJ, de Coo IF, Hendrickx AT, Busch HF, de Jong G, Scholte HR, Smeets HJ (October 2004). "Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene". Neuromuscular Disorders. 14 (10): 683–8. doi:10.1016/j.nmd.2004.06.004. PMID 15351426. S2CID 38721676.

External links

Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW (February 2013). "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. doi:10.1016/j.jns.2012.12.003. PMC 3560033. PMID 23273904.
Ballhausen D, Guerry F, Hahn D, Schaller A, Nuoffer JM, Bonafé L, Jeannet PY, Jacquemont S (December 2010). "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. doi:10.1007/s10545-010-9098-2. PMID 20458543. S2CID 24006011.
Blakely EL, de Silva R, King A, Schwarzer V, Harrower T, Dawidek G, Turnbull DM, Taylor RW (May 2005). "LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation". European Journal of Human Genetics. 13 (5): 623–7. doi:10.1038/sj.ejhg.5201363. PMID 15657614.
Ogle RF, Christodoulou J, Fagan E, Blok RB, Kirby DM, Seller KL, Dahl HH, Thorburn DR (January 1997). "Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin". The Journal of Pediatrics. 130 (1): 138–45. doi:10.1016/S0022-3476(97)70323-8. PMID 9003864.
Houshmand M, Larsson NG, Oldfors A, Tulinius M, Holme E (March 1996). "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. doi:10.1007/BF02185750. PMID 8786060. S2CID 6688307.
Suzuki Y, Nishimaki K, Taniyama M, Muramatsu T, Atsumi Y, Matsuoka K, Ohta S (March 2004). "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. doi:10.1016/j.diabres.2003.10.024. PMID 14757294.
Huang CC, Chu CC, Pang CY, Wei YH (February 1999). "Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS syndrome". Acta Neurologica Scandinavica. 99 (2): 125–9. doi:10.1111/j.1600-0404.1999.tb00670.x. PMID 10071173. S2CID 12099444.
Iwanaga R, Koga Y, Aramaki S, Kato S, Kato H (February 2001). "Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy". Acta Neuropathologica. 101 (2): 179–84. doi:10.1007/s004010000266. PMID 11271374. S2CID 1970758.
Nishigaki Y, Tadesse S, Bonilla E, Shungu D, Hersh S, Keats BJ, Berlin CI, Goldberg MF, Vockley J, DiMauro S, Hirano M (May 2003). "A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome". Neuromuscular Disorders. 13 (4): 334–40. doi:10.1016/S0960-8966(02)00283-3. PMID 12868503. S2CID 53265571.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[pmid7219534-1] 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 (April 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID 7219534. S2CID 4355527.

[entrez-2] "MT-TI mitochondrially encoded tRNA isoleucine [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.

[3] "tRNA / transfer RNA". Learn Science at Scitable.

[:0-4] Bulduk BK, Kiliç HB, Bekircan-Kurt CE, Haliloğlu G, Erdem Özdamar S, Topaloğlu H, Kocaefe YÇ (March 2020). "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. doi:10.1089/gtmb.2019.0079. PMID 32167396. S2CID 212693790.

[pmid10660592-5] Yasukawa T, Suzuki T, Ueda T, Ohta S, Watanabe K (February 2000). "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. doi:10.1074/jbc.275.6.4251. PMID 10660592.

[GHR-6] "MT-TH gene". Genetics Home Reference. This article incorporates text from this source, which is in the public domain.

[pmid17587249-7] Finsterer J (July 2007). "Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation". Acta Neurologica Scandinavica. 116 (1): 1–14. doi:10.1111/j.1600-0404.2007.00836.x. PMID 17587249. S2CID 43823627.

[pmid1360090-8] Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC (December 1992). "Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA". Lancet. 340 (8832): 1376–9. doi:10.1016/0140-6736(92)92560-3. PMID 1360090. S2CID 34540249.

[9] Mazzaccara C, Iafusco D, Liguori R, Ferrigno M, Galderisi A, Vitale D, et al. (2012-04-19). "Mitochondrial diabetes in children: seek and you will find it". PLOS ONE. 7 (4): e34956. Bibcode:2012PLoSO...734956M. doi:10.1371/journal.pone.0034956. PMC 3334935. PMID 22536343. 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.

[10] Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N (April 1998). "Novel mitochondrial DNA mutation in tRNA(Lys) (8296A→G) associated with diabetes". Biochemical and Biophysical Research Communications. 245 (2): 523–7. doi:10.1006/bbrc.1998.8437. PMID 9571188.

[11] van den Bosch BJ, de Coo IF, Hendrickx AT, Busch HF, de Jong G, Scholte HR, Smeets HJ (October 2004). "Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene". Neuromuscular Disorders. 14 (10): 683–8. doi:10.1016/j.nmd.2004.06.004. PMID 15351426. S2CID 38721676.

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