MT-RNR1

Structure

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

Function

The MT-RNR1 gene encodes for an rRNA 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.

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.

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.

Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. Mutations of 1494CT, 1555AG, and 1095TC in the MT-RNR1 gene have been identified to cause the hearing loss.

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. A 9952GA mutation was found in a patient with the deficiency.

References

References

1. (April 1981). "Sequence and organization of the human mitochondrial genome". Nature.
2. (July 1980). "Distinctive sequence of human mitochondrial ribosomal RNA genes". Nature.
3. (March 2006). "Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment". Biochemical and Biophysical Research Communications.
4. (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.
5. (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.
6. (June 2006). "A reappraisal of complete mtDNA variation in East Asian families with hearing impairment". Human Genetics.
7. "Cytochrome c oxidase deficiency".
8. (July 1998). "Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA". American Journal of Human Genetics.