MT-RNR1

{{Short description|SSU rRNA of the mitochondrial ribosome}} {{protein |Name=mitochondrially encoded 12S RNA |caption= |image= |width= |HGNCid=7470 |Symbol=MT-RNR1 |AltSymbols=MTRNR1 |EntrezGene= 4549 |OMIM= |RefSeq= |UniProt= |PDB= |ECnumber= |Chromosome=MT |Arm= |Band= |LocusSupplementaryData= }} [[File:Map of the human mitochondrial genome.svg|thumb|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).]]

'''Mitochondrially encoded 12S ribosomal RNA''' (often abbreviated as '''12S''' or '''12S rRNA''') is the [[SSU rRNA]] of the [[mitochondrial ribosome]]. In humans, 12S is encoded by the ''MT-RNR1'' [[gene]] and is 959 [[nucleotides]] long.<ref>{{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 = 457–465 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 | bibcode = 1981Natur.290..457A | s2cid = 4355527 }}</ref><ref name = "uniprot0"/><ref name = "uniprot"/> 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 [[MT-RNR2|16S]] rRNAs. The 12S rRNA is the mitochondrial homologue of the [[16S ribosomal RNA|prokaryotic 16S]] and [[18S ribosomal RNA|eukaryotic nuclear 18S]] ribosomal RNAs.<ref>{{cite journal | vauthors = Eperon IC, Anderson S, Nierlich DP | title = Distinctive sequence of human mitochondrial ribosomal RNA genes | journal = Nature | volume = 286 | issue = 5772 | pages = 460–467 | date = July 1980 | pmid = 6157106 | doi = 10.1038/286460a0 | bibcode = 1980Natur.286..460E | s2cid = 4262269 }}</ref> Mutations in the MT-RNR1 gene may be associated with hearing loss.<ref name="pmid16458854">{{cite journal | vauthors = Ballana E, Morales E, Rabionet R, Montserrat B, Ventayol M, Bravo O, Gasparini P, Estivill X | title = Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment | journal = Biochemical and Biophysical Research Communications | volume = 341 | issue = 4 | pages = 950–957 | date = March 2006 | pmid = 16458854 | doi = 10.1016/j.bbrc.2006.01.049 | bibcode = 2006BBRC..341..950B }}</ref> The rRNA gene also encodes a peptide '''[[MOTS-c]]''', also known as '''Mitochondrial-derived peptide MOTS-c''' or '''Mitochondrial [[open reading frame]] of the 12S rRNA-c'''.

== Structure == The ''MT-RNR1'' gene is located on the [[Locus (genetics)|p arm]] of the [[mitochondrial DNA]] at position 12 and it spans 953 base pairs.<ref name="entrez">

{{cite web |title=MT-RNR1 mitochondrially encoded 12S RNA [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/4549 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>

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

{{Cite web|url= https://www.uniprot.org/uniprot/A0A0C5B5G6 |title=MT-RNR1 - Mitochondrial-derived peptide MOTS-c - Homo sapiens (Human) - MT-RNR1 gene & protein|access-date=2018-08-28}}{{CC-notice|cc=by4 | url=https://www.uniprot.org/uniprot/A0A0C5B5G6 | work = UniProt }}

</ref><ref name = "uniprot0">

{{cite journal | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}

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== Clinical significance == === Nonsyndromic hearing loss and deafness, mitochondrial === Pathogenic mutations in the ''MT-RNR1'' gene have been found to cause late-onset [[Nonsyndromic deafness|Mitochondrial nonsyndromic hearing loss and deafness]] with predisposed [[aminoglycoside]] [[ototoxicity|ototoxicities]].<ref>

{{cite book |last1=Usami |first1=Shin-ichi |last2=Nishio |first2=Shin-ya |title=GeneReviews® |date=1993 |publisher=University of Washington, Seattle |url=https://www.ncbi.nlm.nih.gov/books/NBK1422/ |chapter=Nonsyndromic Hearing Loss and Deafness, Mitochondrial|pmid=20301595 }}</ref> [[Nonsyndromic deafness]] is characterized by a partial or total [[Sensorineural hearing loss|sensorineural hearing loss (SNHL)]] of variable onset and severity that is not associated with other signs and symptoms.<ref>

{{cite web |last1=Reference |first1=Genetics Home |title=Nonsyndromic hearing loss |url=https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss/ |website=Genetics Home Reference |language=en}}

</ref> Most forms of nonsyndromic deafness are associated with permanent [[hearing loss]] caused by damage to structures in the [[inner ear]].<ref name= "uniprot0"/><ref name= "uniprot"/> Mutations of 1494C>T, 1555A>G, and 1095T>C in the ''MT-RNR1'' gene have been identified to cause the [[hearing loss]].<ref>{{cite journal | vauthors = Li R, Greinwald JH, Yang L, Choo DI, Wenstrup RJ, Guan MX | title = Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss | journal = Journal of Medical Genetics | volume = 41 | issue = 8 | pages = 615–620 | date = August 2004 | pmid = 15286157 | doi = 10.1136/jmg.2004.020230 | pmc = 1735864 }}</ref><ref>{{cite journal | vauthors = Zhao H, Li R, Wang Q, Yan Q, Deng JH, Han D, Bai Y, Young WY, Guan MX | title = 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 | journal = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 139–152 | date = January 2004 | pmid = 14681830 | doi = 10.1086/381133 | pmc = 1181901 }}</ref><ref>{{cite journal | vauthors = Yao YG, Salas A, Bravi CM, Bandelt HJ | title = A reappraisal of complete mtDNA variation in East Asian families with hearing impairment | journal = Human Genetics | volume = 119 | issue = 5 | pages = 505–515 | date = June 2006 | pmid = 16528519 | doi = 10.1007/s00439-006-0154-9 | s2cid = 21173284 }}</ref>

=== 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]].<ref>{{cite web |last1=Reference |first1=Genetics Home |title=Cytochrome c oxidase deficiency |url=https://medlineplus.gov/genetics/condition/cytochrome-c-oxidase-deficiency/ |website=Genetics Home Reference |language=en}}{{PD-notice}}</ref> A 9952G>A mutation was found in a patient with the deficiency.<ref>{{cite journal | vauthors = Hanna MG, Nelson IP, Rahman S, Lane RJ, Land J, Heales S, Cooper MJ, Schapira AH, Morgan-Hughes JA, Wood NW | title = Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA | journal = American Journal of Human Genetics | volume = 63 | issue = 1 | pages = 29–36 | date = July 1998 | pmid = 9634511 | doi = 10.1086/301910 | pmc = 1377234 }}</ref>

== References == {{Reflist}}

== External links == * [https://www.ncbi.nlm.nih.gov/books/NBK1422/ GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, Mitochondrial]

{{DEFAULTSORT:Mt-Rnr1}} [[Category:Ribosomal RNA]]