MT-TP explained

mitochondrially encoded tRNA proline
Hgncid:	7494
Symbol:	MT-TP
Altsymbols:	MTTP
Entrezgene:	4571
Refseq:	NC_001807
Chromosome:	MT

Mitochondrially encoded tRNA proline also known as MT-TP is a transfer RNA that in humans is encoded by the mitochondrial MT-TP gene.^[1]

Structure

The MT-TP gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 68 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-TP is a small 68 nucleotide RNA (human mitochondrial map position 15956-16023) that transfers the amino acid proline to a growing polypeptide chain at the ribosome site of protein synthesis during translation. MT-TP is responsible for coding the microsomal triglyceride transfer protein, which is required for the synthesis of beta-lipoproteins in the liver and intestine. Beta-lipoproteins are essential in fat, cholesterol, and fat-soluble vitamin transport from the intestine to the bloodstream for absorption.^[4]

Clinical significance

Abetalipoproteinemia

Mutations in MT-TP have been associated with abetalipoproteinemia. Abetalipoproteinemia is an inherited disorder characterized by an impaired absorption of fats and certain vitamins from the diet. Mutations in MT-TP cause an impaired microsomal triglyceride transfer protein and lead to reduced or absent beta-lipoprotein. The dysfunction of the microsomal triglyceride transfer protein then results in insufficient levels of fats, cholesterol, and vitamins, which are necessary for growth and development.^[4] Therefore, clinical manifestations of abetalipoproteinemia include impaired weight gain and growth, failure to thrive, diarrhea, and steatorrhea. Mutations of GLY865TER,^[5] SER590ILE,^[6] ASN780TYR,^[7] ARG540HIS,^[8] IVS9AS,^[9] and ARG215TER^[10] of the MT-TP gene have been found in patients with the disease.

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 G15975A mutation has been found in a patient with the deficiency. In addition, MT-TP mutations have been associated with late-onset ataxia, retinitis, pigmentosa, deafness, leukoencephalopathy, and complex IV deficiency.^{[11] [12]}

Notes and 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 . Sequence and organization of the human mitochondrial genome . Nature . 290 . 5806 . 457–65 . April 1981 . 7219534 . 10.1038/290457a0 . 1981Natur.290..457A . 4355527 .
2. Web site: MT-TN mitochondrially encoded tRNA asparagine [Homo sapiens (human)] - Gene - NCBI ]. www.ncbi.nlm.nih.gov . en.
3. Web site: tRNA / transfer RNA . Learn Science at Scitable .
4. Reference . Genetics Home . Abetalipoproteinemia . Genetics Home Reference . en.
5. Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T . Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient . Molecular Genetics and Metabolism . 90 . 4 . 453–7 . April 2007 . 17275380 . 10.1016/j.ymgme.2006.12.010 .
6. Al-Shali K, Wang J, Rosen F, Hegele RA . Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia . Clinical Genetics . 63 . 2 . 135–8 . February 2003 . 12630961 . 10.1046/j.0009-9163.2002.00175.x . 22241594 .
7. Ohashi K, Ishibashi S, Osuga J, Tozawa R, Harada K, Yahagi N, Shionoiri F, Iizuka Y, Tamura Y, Nagai R, Illingworth DR, Gotoda T, Yamada N . Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia . Journal of Lipid Research . 41 . 8 . 1199–204 . August 2000 . 10.1016/S0022-2275(20)33426-X . 10946006 . free .
8. Rehberg EF, Samson-Bouma ME, Kienzle B, Blinderman L, Jamil H, Wetterau JR, Aggerbeck LP, Gordon DA . A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase . The Journal of Biological Chemistry . 271 . 47 . 29945–52 . November 1996 . 8939939 . 10.1074/jbc.271.47.29945 . free .
9. Yang XP, Inazu A, Yagi K, Kajinami K, Koizumi J, Mabuchi H . Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene . Arteriosclerosis, Thrombosis, and Vascular Biology . 19 . 8 . 1950–5 . August 1999 . 10446076 . 10.1161/01.ATV.19.8.1950 . free .
10. Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, Gil CM, Turck CW, Bouma ME, Rader DJ . Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia . Nature . 365 . 6441 . 65–9 . September 1993 . 8361539 . 10.1038/365065a0 . 1993Natur.365...65S . 4334532 .
11. Da Pozzo P, Cardaioli E, Malfatti E, Gallus GN, Malandrini A, Gaudiano C, Berti G, Invernizzi F, Zeviani M, Federico A . A novel mutation in the mitochondrial tRNA(Pro) gene associated with late-onset ataxia, retinitis pigmentosa, deafness, leukoencephalopathy and complex I deficiency . European Journal of Human Genetics . 17 . 8 . 1092–6 . August 2009 . 19223931 . 2986557 . 10.1038/ejhg.2009.12 .
12. Blakely EL, Trip SA, Swalwell H, He L, Wren DR, Rich P, Turnbull DM, Omer SE, Taylor RW . A new mitochondrial transfer RNAPro gene mutation associated with myoclonic epilepsy with ragged-red fibers and other neurological features . Archives of Neurology . 66 . 3 . 399–402 . March 2009 . 19273760 . 10.1001/archneurol.2008.576 . free .