Mitochondrially encoded 12S ribosomal RNA (MT-RNR1)

Mitochondrially encoded 12S ribosomal RNA, encoded by the MT-RNR1 gene, is a highly conserved non-coding RNA component of the small subunit of the mitochondrial ribosome, essential for mitochondrial protein translation[1][5]. Uniquely, this gene's sequence also contains a short open reading frame encoding a 16-amino acid peptide called MOTS-c, which acts as a metabolic regulator and has been implicated in glucose metabolism, insulin sensitivity, stress response, and endurance—especially in skeletal muscle[1][2][4][6]. Pathogenic mutations in MT-RNR1 are a major cause of maternally inherited, nonsyndromic hearing loss (especially following aminoglycoside exposure) and can be biomarkers for genetic susceptibility to drug-induced ototoxicity[1][3]. MOTS-c, derived from MT-RNR1, is under investigation as a therapeutic for metabolic diseases including diabetes and cardiomyopathies, but its clinical use and safety are unproven[2][4]. The rRNA itself is not a typical druggable target; it serves more as a genetic risk locus and as the origin for MOTS-c, which may be a bona fide therapeutic target in the future[1][2][4].

Other names

12S rRNA12SMitochondrial-derived peptide MOTS-cMOTS-cMitochondrial open reading frame of the 12S rRNA-cMitochondrial open-reading-frame of the twelve S rRNA type-c

For aminoglycosides: Bind to mitochondrial ribosomal RNA, causing misreading and ototoxicity in individuals with specific mutations[3] For MOTS-c: Modulates cellular energy utilization, inhibits folate cycle and de novo purine biosynthesis, activates AMPK, enhances glucose uptake and insulin sensitivity[1][2][6] For MOTS-c: Acts as metabolic regulator and stress response modulator[2][4][6]