View source for MT-TL1

{{infobox protein
|Name=mitochondrially encoded tRNA leucine 1 (UUA/G)
|caption=
|image=
|width=
|HGNCid=7490
|Symbol=MT-TL1
|AltSymbols=MTTL1
|EntrezGene=4567
|OMIM=590050
|RefSeq= NC_001807
|UniProt=
|PDB=
|ECnumber=
|Chromosome=MT
|Arm=
|Band=
|LocusSupplementaryData=
}}
'''Mitochondrially encoded tRNA leucine 1 (UUA/G)''' also known as '''MT-TL1''' is a [[transfer RNA]] which in humans is encoded by the [[mitochondrion|mitochondrial]] ''MT-TL1'' [[gene]].<ref name="pmid7219534">{{cite journal | vauthors = 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 | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–65 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 }}</ref>

== Structure ==
The ''MT-TL1'' gene is located on the [[Locus (genetics)|p arm]] of the [[mitochondrial DNA]] at position 12 and it spans 75 base pairs.<ref name = "entrez">
{{cite web |title=MT-TI mitochondrially encoded tRNA isoleucine [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=4565 |website=www.ncbi.nlm.nih.gov |language=en}}</ref> The structure of a [[tRNA]] molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed [[clover]].<ref>{{cite web |title=tRNA / transfer RNA | work = Learn Science at Scitable |url=https://www.nature.com/scitable/definition/trna-transfer-rna-256 }}</ref>

== 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 [[ribosomal|ribosome]] site of [[protein]] synthesis during [[translation (genetics)|translation]].

==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 ([[mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes|MELAS]]).<ref name="pmid10660592">{{cite journal | vauthors = Yasukawa T, Suzuki T, Ueda T, Ohta S, Watanabe K | title = Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 6 | pages = 4251–7 | date = February 2000 | pmid = 10660592 | doi = 10.1074/jbc.275.6.4251 }}</ref> 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]].<ref name = "GHR">{{cite web |title=MT-TH gene |url=https://ghr.nlm.nih.gov/gene/MT-TH#conditions |website=Genetics Home Reference |language=en}}{{PD-notice}}</ref> A common mutation is A3243G. This mutation has been theorized to be associated with several other [[mitochondrial disease]]s,<ref name="pmid17587249">{{cite journal | vauthors = Finsterer J | title = Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation | journal = Acta Neurologica Scandinavica | volume = 116 | issue = 1 | pages = 1–14 | date = July 2007 | pmid = 17587249 | doi = 10.1111/j.1600-0404.2007.00836.x }}</ref> including [[diabetes mellitus and deafness]].<ref name="pmid1360090">{{cite journal | vauthors = Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC | title = Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA | journal = Lancet | volume = 340 | issue = 8832 | pages = 1376–9 | date = December 1992 | pmid = 1360090 | doi = 10.1016/0140-6736(92)92560-3 }}</ref><ref>{{cite journal | vauthors = Mazzaccara C, Iafusco D, Liguori R, Ferrigno M, Galderisi A, Vitale D, Simonelli F, Landolfo P, Prisco F, Masullo M, Sacchetti L | display-authors = 6 | title = Mitochondrial diabetes in children: seek and you will find it | journal = PLOS One | volume = 7 | issue = 4 | pages = e34956 | date = 2012-04-19 | pmid = 22536343 | pmc = 3334935 | doi = 10.1371/journal.pone.0034956 | quote = 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. | last-author-amp = yes }}</ref> [[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.<ref>{{cite journal | vauthors = Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N | title = Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes | journal = Biochemical and Biophysical Research Communications | volume = 245 | issue = 2 | pages = 523–7 | date = April 1998 | pmid = 9571188 | doi = 10.1006/bbrc.1998.8437 }}</ref>

===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.<ref>{{cite journal | vauthors = van den Bosch BJ, de Coo IF, Hendrickx AT, Busch HF, de Jong G, Scholte HR, Smeets HJ | title = Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene | journal = Neuromuscular Disorders | volume = 14 | issue = 10 | pages = 683–8 | date = October 2004 | pmid = 15351426 | doi = 10.1016/j.nmd.2004.06.004 }}</ref>

== See also ==
* [[Mitochondrial DNA]]

== References ==
{{reflist}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1173/  GeneReviews/NCBI/NIH/UW entry on Mitochondrial DNA-Associated Leigh Syndrome and NARP]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=melas  GeneReviews/NCBI/NIH/UW entry on MELAS]

==Further reading==
{{refbegin | 2}}
* {{cite journal | vauthors = Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW | title = The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease | journal = Journal of the Neurological Sciences | volume = 325 | issue = 1-2 | pages = 165–9 | date = February 2013 | pmid = 23273904 | doi = 10.1016/j.jns.2012.12.003 }}
* {{cite journal | vauthors = Ballhausen D, Guerry F, Hahn D, Schaller A, Nuoffer JM, Bonafé L, Jeannet PY, Jacquemont S | title = Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study | journal = Journal of Inherited Metabolic Disease | volume = 33 Suppl 3 | pages = S219-26 | date = December 2010 | pmid = 20458543 | doi = 10.1007/s10545-010-9098-2 }}
* {{cite journal | vauthors = Blakely EL, de Silva R, King A, Schwarzer V, Harrower T, Dawidek G, Turnbull DM, Taylor RW | title = LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation | journal = European Journal of Human Genetics | volume = 13 | issue = 5 | pages = 623–7 | date = May 2005 | pmid = 15657614 | doi = 10.1038/sj.ejhg.5201363 }}
* {{cite journal | vauthors = Ogle RF, Christodoulou J, Fagan E, Blok RB, Kirby DM, Seller KL, Dahl HH, Thorburn DR | title = Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin | journal = The Journal of Pediatrics | volume = 130 | issue = 1 | pages = 138–45 | date = January 1997 | pmid = 9003864 }}
* {{cite journal | vauthors = Houshmand M, Larsson NG, Oldfors A, Tulinius M, Holme E | title = 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 | journal = Human Genetics | volume = 97 | issue = 3 | pages = 269–73 | date = March 1996 | pmid = 8786060 }}
* {{cite journal | vauthors = Suzuki Y, Nishimaki K, Taniyama M, Muramatsu T, Atsumi Y, Matsuoka K, Ohta S | title = Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation | journal = Diabetes Research and Clinical Practice | volume = 63 | issue = 3 | pages = 225–9 | date = March 2004 | pmid = 14757294 }}
* {{cite journal | vauthors = Huang CC, Chu CC, Pang CY, Wei YH | title = Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS syndrome | journal = Acta Neurologica Scandinavica | volume = 99 | issue = 2 | pages = 125–9 | date = February 1999 | pmid = 10071173 }}
* {{cite journal | vauthors = Iwanaga R, Koga Y, Aramaki S, Kato S, Kato H | title = Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy | journal = Acta Neuropathologica | volume = 101 | issue = 2 | pages = 179–84 | date = February 2001 | pmid = 11271374 }}
* {{cite journal | vauthors = Nishigaki Y, Tadesse S, Bonilla E, Shungu D, Hersh S, Keats BJ, Berlin CI, Goldberg MF, Vockley J, DiMauro S, Hirano M | title = A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome | journal = Neuromuscular Disorders | volume = 13 | issue = 4 | pages = 334–40 | date = May 2003 | pmid = 12868503 }}
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