Human mitochondrial 12S ribosomal RNA (MT-RNR1) (MT-RNR1)

Human mitochondrial 12S ribosomal RNA (MT-RNR1) is a structural and functional component of the small (28S) subunit of the mitochondrial ribosome, essential for the translation of the 13 proteins encoded by the mitochondrial genome (NCBI Gene: 4549). These proteins are critical components of the oxidative phosphorylation complexes required for ATP production. MT-RNR1 is a significant pharmacological target, particularly as an off-target for aminoglycoside antibiotics like gentamicin and streptomycin. Aminoglycosides bind to the decoding A-site of the 12S rRNA, a site that is evolutionarily conserved from bacteria. In individuals with specific mitochondrial DNA mutations, such as m.1555A>G, the human mitochondrial rRNA becomes more similar to bacterial 16S rRNA, increasing the binding affinity of these drugs (PMID: 8464480). This interaction leads to the inhibition of mitochondrial protein synthesis, resulting in the death of hair cells in the inner ear and subsequent permanent hearing loss (OMIM: 561000). Consequently, MT-RNR1 is a key focus in pharmacogenetics and the prevention of drug-induced ototoxicity.

Other names

12S rRNAMTRNR1Mitochondrially encoded 12S RNASmall subunit ribosomal RNA12S ribosomal RNA

Aminoglycosides bind to the decoding A-site of the 12S rRNA, causing mistranslation or inhibition of mitochondrial protein synthesis, which leads to cellular toxicity in the inner ear (PMID: 10746561).