MT-TP

Last updated
mitochondrially encoded tRNA proline
Identifiers
SymbolMT-TP
Alt. symbolsMTTP
NCBI gene 4571
HGNC 7494
RefSeq NC_001807
Other data
Locus Chr. 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]

Contents

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]

Related Research Articles

Abetalipoproteinemia Medical condition

Abetalipoproteinemia is a disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.

Retinitis pigmentosa Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreased peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often in childhood.

Neuropathy, ataxia, and retinitis pigmentosa Medical condition

Neuropathy, ataxia, and retinitis pigmentosa, also known as NARP syndrome, is a rare disease with mitochondrial inheritance that causes a variety of signs and symptoms chiefly affecting the nervous system Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs ; muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye. In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.

MT-RNR1

Mitochondrially encoded 12S ribosomal RNA, also known as Mitochondrial-derived peptide MOTS-c or Mitochondrial open reading frame of the 12S rRNA-c is the SSU rRNA of the mitochondrial ribosome. In humans, 12S is encoded by the MT-RNR1 gene and is 959 nucleotides long. MT-RNR1 is one of the 37 genes contained in animal mitochondria genomes. Their 2 rRNA, 22 tRNA and 13 mRNA genes are very useful in phylogenetic studies, in particular the 12S and 16S rRNAs. The 12S rRNA is the mitochondrial homologue of the prokaryotic 16S and eukaryotic nuclear 18S ribosomal RNAs. Mutations in the MT-RNR1 gene may be associated with hearing loss.

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.

Microsomal triglyceride transfer protein

Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP gene.

MT-CYB A mitochondrial protein-coding gene whose product is involved in the respiratory chain

Cytochrome b is a protein that in humans is encoded by the MT-CYB gene. Its gene product is a subunit of the respiratory chain protein ubiquinol–cytochrome c reductase, which consists of the products of one mitochondrially encoded gene, MT-CYB, and ten nuclear genes—UQCRC1, UQCRC2, CYC1, UQCRFS1, UQCRB, "11kDa protein", UQCRH, Rieske protein presequence, "cyt c1 associated protein", and Rieske-associated protein.

Chylomicron retention disease

Chylomicron retention disease is a disorder of fat absorption. It is associated with SAR1B. Mutations in SAR1B prevent the release of chylomicrons in the circulation which leads to nutritional and developmental problems. It is a rare autosomal recessive disorder with around 40 cases reported worldwide. Since the disease allele is recessive, parents usually do not show symptoms.

Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene.

Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene. MT-TE is a small 69 nucleotide RNA that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation.

Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene.

Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.

Mitochondrially encoded tRNA leucine 2 (CUN) also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene.

Mitochondrially encoded tRNA asparagine also known as MT-TN is a transfer RNA which in humans is encoded by the mitochondrial MT-TN gene.

Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene.

Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene.

Mitochondrially encoded tRNA tryptophan also known as MT-TW is a transfer RNA which in humans is encoded by the mitochondrial MT-TW gene.

Mitochondrially encoded tRNA tyrosine also known as MT-TY is a transfer RNA which in humans is encoded by the mitochondrial MT-TY gene.

Retinal degeneration (rhodopsin mutation)

Retinal degeneration is a retinopathy which consists in the deterioration of the retina caused by the progressive death of its cells. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P., or disease. These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.

Locus heterogeneity occurs when mutations at multiple genomic loci are capable of producing the same phenotype, and each individual mutation is sufficient to cause the specific phenotype independently. Locus heterogeneity should not be confused with allelic heterogeneity, in which a single phenotype can be produced by multiple mutations, all of which are at the same locus on a chromosome. Likewise, it should not be confused with phenotypic heterogeneity, in which different phenotypes arise among organisms with identical genotypes and environmental conditions. Locus heterogeneity and allelic heterogeneity are the two components of genetic heterogeneity.

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. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID   7219534. S2CID   4355527.
  2. ↑ "MT-TN mitochondrially encoded tRNA asparagine [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  3. ↑ "tRNA / transfer RNA". Learn Science at Scitable.
  4. 1 2 Reference, Genetics Home. "Abetalipoproteinemia". Genetics Home Reference.
  5. ↑ Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T (April 2007). "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. doi:10.1016/j.ymgme.2006.12.010. PMID   17275380.
  6. ↑ Al-Shali K, Wang J, Rosen F, Hegele RA (February 2003). "Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia". Clinical Genetics. 63 (2): 135–8. doi:10.1046/j.0009-9163.2002.00175.x. PMID   12630961. S2CID   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 (August 2000). "Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia". Journal of Lipid Research. 41 (8): 1199–204. doi: 10.1016/S0022-2275(20)33426-X . PMID   10946006.
  8. ↑ Rehberg EF, Samson-Bouma ME, Kienzle B, Blinderman L, Jamil H, Wetterau JR, Aggerbeck LP, Gordon DA (November 1996). "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. doi: 10.1074/jbc.271.47.29945 . PMID   8939939.
  9. ↑ Yang XP, Inazu A, Yagi K, Kajinami K, Koizumi J, Mabuchi H (August 1999). "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. doi: 10.1161/01.ATV.19.8.1950 . PMID   10446076.
  10. ↑ Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, Gil CM, Turck CW, Bouma ME, Rader DJ (September 1993). "Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia". Nature. 365 (6441): 65–9. Bibcode:1993Natur.365...65S. doi:10.1038/365065a0. PMID   8361539. S2CID   4334532.
  11. ↑ Da Pozzo P, Cardaioli E, Malfatti E, Gallus GN, Malandrini A, Gaudiano C, Berti G, Invernizzi F, Zeviani M, Federico A (August 2009). "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. doi:10.1038/ejhg.2009.12. PMC   2986557 . PMID   19223931.
  12. ↑ Blakely EL, Trip SA, Swalwell H, He L, Wren DR, Rich P, Turnbull DM, Omer SE, Taylor RW (March 2009). "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. doi: 10.1001/archneurol.2008.576 . PMID   19273760.

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