MT-RNR1

Mitochondrially encoded 12S ribosomal RNA (often abbreviated as 12S or 12S rRNA), also known as Mitochondrial-derived peptide MOTS-c or Mitochondrial open reading frame of the 12S rRNA-c is a component of the small subunit (SSU) of the mitochondrial ribosome. In humans, 12S is encoded by the MT-RNR1 gene and is 959 nucleotides long.[1][2][3] 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.[4] Mutations in the MT-RNR1 gene may be associated with hearing loss.[5]

mitochondrially encoded 12S RNA
Identifiers
Symbol	MT-RNR1
Alt. symbols	MTRNR1
NCBI gene	4549
HGNC	7470
Other data
Locus	Chr. MT

Location of the MT-RNR1 gene on the H strand of the human mitochondrial genome. MT-RNR1, or RRNS, is one of the two mitochondrial ribosomal RNA genes (blue boxes).

Structure

The MT-RNR1 gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 953 base pairs.[6]

Function

The MT-RNR1 gene encodes for a protein responsible for regulating insulin sensitivity and metabolic homeostasis. The protein acts as an inhibitor of the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK). The protein also protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity.[3][2]

Clinical significance

Nonsyndromic Hearing Loss and Deafness, Mitochondrial

Pathogenic mutations in the MT-RNR1 gene have been found to cause late-onset Mitochondrial Nonsyndromic Hearing Loss and Deafness with predisposed aminoglycoside ototoxicities.[7] Nonsyndromic Deafness is characterized by a partial or total sensorineural hearing loss (SNHL) of variable onset and severity that is not associated with other signs and symptoms.[8] Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear.[2][3] Mutations of 1494C>T, 1555A>G, and 1095T>C in the MT-RNR1 gene have been identified to cause the hearing loss.[9][10][11]

Complex IV Deficiency

MT-RNR1 mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[12] A 9952G>A mutation was found in a patient with the deficiency.[13]

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): 457–465. doi:10.1038/290457a0. PMID 7219534.
2. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
3. "MT-RNR1 - Mitochondrial-derived peptide MOTS-c - Homo sapiens (Human) - MT-RNR1 gene & protein". Retrieved 2018-08-28. This article incorporates text available under the CC BY 4.0 license.
4. Eperon IC, Anderson S, Nierlich DP (July 1980). "Distinctive sequence of human mitochondrial ribosomal RNA genes". Nature. 286 (5772): 460–467. doi:10.1038/286460a0. PMID 6157106.
5. Ballana E, Morales E, Rabionet R, Montserrat B, Ventayol M, Bravo O, Gasparini P, Estivill X (March 2006). "Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment". Biochemical and Biophysical Research Communications. 341 (4): 950–957. doi:10.1016/j.bbrc.2006.01.049. PMID 16458854.
6. "MT-RNR1 mitochondrially encoded 12S RNA [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
7. Usami, Shin-ichi; Nishio, Shin-ya (1993). "Nonsyndromic Hearing Loss and Deafness, Mitochondrial". GeneReviews®. University of Washington, Seattle.
8. Reference, Genetics Home. "Nonsyndromic hearing loss". Genetics Home Reference.
9. Li R, Greinwald JH, Yang L, Choo DI, Wenstrup RJ, Guan MX (August 2004). "Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss". Journal of Medical Genetics. 41 (8): 615–620. doi:10.1136/jmg.2004.020230. PMC 1735864. PMID 15286157.
10. Zhao H, Li R, Wang Q, Yan Q, Deng JH, Han D, Bai Y, Young WY, Guan MX (January 2004). "Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family". American Journal of Human Genetics. 74 (1): 139–152. doi:10.1086/381133. PMC 1181901. PMID 14681830.
11. Yao YG, Salas A, Bravi CM, Bandelt HJ (June 2006). "A reappraisal of complete mtDNA variation in East Asian families with hearing impairment". Human Genetics. 119 (5): 505–515. doi:10.1007/s00439-006-0154-9. PMID 16528519.
12. Reference, Genetics Home. "Cytochrome c oxidase deficiency". Genetics Home Reference. This article incorporates text from this source, which is in the public domain.
13. Hanna MG, Nelson IP, Rahman S, Lane RJ, Land J, Heales S, Cooper MJ, Schapira AH, Morgan-Hughes JA, Wood NW (July 1998). "Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA". American Journal of Human Genetics. 63 (1): 29–36. doi:10.1086/301910. PMC 1377234. PMID 9634511.

External links

• GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, Mitochondrial

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