Biology:MT-TL1
| 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 includemuscle 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]
See also
References
- ↑ "Sequence and organization of the human mitochondrial genome". Nature 290 (5806): 457–65. April 1981. doi:10.1038/290457a0. PMID 7219534. Bibcode: 1981Natur.290..457A.
- ↑ "MT-TI mitochondrially encoded tRNA isoleucine [Homo sapiens (human) - Gene - NCBI"] (in en). https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=4565.
- ↑ "tRNA / transfer RNA". Learn Science at Scitable. https://www.nature.com/scitable/definition/trna-transfer-rna-256.
- ↑ 4.0 4.1 "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. doi:10.1089/gtmb.2019.0079. PMID 32167396.
- ↑ "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. doi:10.1074/jbc.275.6.4251. PMID 10660592.
- ↑ "MT-TH gene" (in en). https://ghr.nlm.nih.gov/gene/MT-TH#conditions.
This article incorporates text from this source, which is in the public domain.
- ↑ "Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation". Acta Neurologica Scandinavica 116 (1): 1–14. July 2007. doi:10.1111/j.1600-0404.2007.00836.x. PMID 17587249.
- ↑ "Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA". Lancet 340 (8832): 1376–9. December 1992. doi:10.1016/0140-6736(92)92560-3. PMID 1360090.
- ↑ "Mitochondrial diabetes in children: seek and you will find it". PLOS ONE 7 (4): e34956. 2012-04-19. doi:10.1371/journal.pone.0034956. PMID 22536343. Bibcode: 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.".
- ↑ "Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes". Biochemical and Biophysical Research Communications 245 (2): 523–7. April 1998. doi:10.1006/bbrc.1998.8437. PMID 9571188.
- ↑ "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. doi:10.1016/j.nmd.2004.06.004. PMID 15351426.
External links
- GeneReviews/NCBI/NIH/UW entry on Mitochondrial DNA-Associated Leigh Syndrome and NARP
- GeneReviews/NCBI/NIH/UW entry on MELAS
Further reading
- "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. doi:10.1016/j.jns.2012.12.003. PMID 23273904.
- "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. doi:10.1007/s10545-010-9098-2. PMID 20458543. https://serval.unil.ch/notice/serval:BIB_1B93A7D53BDC.
- "LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation". European Journal of Human Genetics 13 (5): 623–7. May 2005. doi:10.1038/sj.ejhg.5201363. PMID 15657614.
- "Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin". The Journal of Pediatrics 130 (1): 138–45. January 1997. doi:10.1016/S0022-3476(97)70323-8. PMID 9003864.
- "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. doi:10.1007/BF02185750. PMID 8786060.
- "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. doi:10.1016/j.diabres.2003.10.024. PMID 14757294.
- "Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS syndrome". Acta Neurologica Scandinavica 99 (2): 125–9. February 1999. doi:10.1111/j.1600-0404.1999.tb00670.x. PMID 10071173.
- "Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy". Acta Neuropathologica 101 (2): 179–84. February 2001. doi:10.1007/s004010000266. PMID 11271374.
- "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. doi:10.1016/S0960-8966(02)00283-3. PMID 12868503.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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