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 the

SSU rRNA Small subunit ribosomal ribonucleic acid (SSU rRNA) is the smaller of the two major RNA components of the ribosome. Associated with a number of ribosomal proteins, the SSU rRNA forms the small subunit of the ribosome. It is encoded by SSU- rDNA. ...

of the

mitochondrial ribosome The mitochondrial ribosome, or mitoribosome, is a protein complex that is active in mitochondria and functions as a riboprotein for translating mitochondrial mRNAs encoded in mtDNA. The mitoribosome is attached to the inner mitochondrial membrane ...

. In humans, 12S is encoded by the ''MT-RNR1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

and is 959

nucleotides Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...

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.

Structure

The ''MT-RNR1'' gene is located on the

p arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...

of the mitochondrial DNA at position 12 and it spans 953 base pairs.

Function

The ''MT-RNR1'' gene encodes for a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

responsible for regulating insulin sensitivity and metabolic

homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...

. 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 Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...

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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

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 Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

ototoxicities.

Nonsyndromic Deafness Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the follow ...

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. Most forms of nonsyndromic deafness are associated with permanent

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken ...

caused by damage to structures in the inner ear. Mutations of 1494C>T, 1555A>G, and 1095T>C in the ''MT-RNR1'' gene have been identified to cause the

Complex IV Deficiency

''MT-RNR1'' mutations have been associated with complex IV deficiency of the

mitochondrial respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...

, also known as the

cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory elect ...

deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including

skeletal muscles Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

, the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

, the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

, or the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. Common clinical manifestations include myopathy,

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...

, and encephalomyopathy,

lactic acidosis Lactic acidosis is a medical condition characterized by a build-up of lactate (especially -lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates d ...

, and hypertrophic cardiomyopathy. A 9952G>A mutation was found in a patient with the deficiency.

References

External links

GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, Mitochondrial
{{DEFAULTSORT:Mt-Rnr1 Ribosomal RNA