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{{protein
{{infobox protein
|Name=mitochondrially encoded tRNA leucine 1 (UUA/G)
|Name=mitochondrially encoded tRNA leucine 1 (UUA/G)
|caption=
|caption=
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|EntrezGene=4567
|EntrezGene=4567
|OMIM=590050
|OMIM=590050
|RefSeq=
|RefSeq= NC_001807
|UniProt=
|UniProt=
|PDB=
|PDB=
|ECnumber=
|ECnumber=
|Chromosome=mitochondria
|Chromosome=MT
|Arm=
|Arm=
|Band=
|Band=
|LocusSupplementaryData=
|LocusSupplementaryData=
}}
}}
'''MT-TL1''' is a mitochondrial gene. It is associated with [[mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes]].
'''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>


One common mutation is A3,243G. This mutation has been theorized to be associated with several other [[mitochondrial disease]],<ref name="pmid17587249">{{cite journal |author=Finsterer J |title=Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation |journal=Acta Neurol. Scand. |volume=116 |issue=1 |pages=1–14 |year=2007 |pmid=17587249 |doi=10.1111/j.1600-0404.2007.00836.x}}</ref> including [[diabetes mellitus and deafness]].<ref name="pmid1360090">{{cite journal |author=Reardon W, Ross RJ, Sweeney MG, ''et al'' |title=Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA |journal=Lancet |volume=340 |issue=8832 |pages=1376–9 |year=1992 |pmid=1360090 |doi=}}</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>


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


==References==
== References ==
{{reflist|2}}
{{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 }}
{{refend}}


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{{Mitochondrial enzymes}}
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Revision as of 17:27, 22 September 2018

mitochondrially encoded tRNA leucine 1 (UUA/G)
Identifiers
SymbolMT-TL1
Alt. symbolsMTTL1
Entrez4567
HUGO7490
OMIM590050
RefSeqNC_001807
Other data
LocusChr. 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.

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).[4] 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.[5] A common mutation is A3243G. This mutation has been theorized to be associated with several other mitochondrial diseases,[6] including diabetes mellitus and deafness.[7][8] Diabetes mellitus and deafness is characterized by diabetes combined with hearing loss, particularly of high pitches. Additional symptoms includemuscle weakness (myopathy) and various problems with a patient's eyes, heart, or kidneys.[9]

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.[10]

See also

References

  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. doi:10.1038/290457a0. PMID 7219534.
  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.
  4. ↑ 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.
  5. ↑ "MT-TH gene". Genetics Home Reference. This article incorporates text from this source, which is in the public domain.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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. 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.
  9. ↑ 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.
  10. ↑ 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.

External links

Further reading

  • 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. 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.
  • 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. 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. PMID 8786060.
  • 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. 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. PMID 10071173.
  • 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. PMID 11271374.
  • 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. PMID 12868503.

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

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