Mitochondrially encoded tRNA leucine 1 (UUR) (MT-TL1)

Mitochondrially encoded tRNA leucine 1 (MT-TL1) is a transfer RNA molecule encoded by the mitochondrial genome (mtDNA) that is essential for the translation of the 13 proteins produced within the mitochondria [1, 2]. It specifically recognizes the UUR (UUA and UUG) codons, facilitating the incorporation of leucine into nascent polypeptide chains during mitochondrial protein synthesis [1]. Mutations in the MT-TL1 gene, most notably the m.3243A>G transition, are the primary genetic cause of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) and Maternally Inherited Diabetes and Deafness (MIDD) [3]. These mutations lead to a deficiency in the taurinomethyluridine modification at the wobble position of the tRNA, which impairs translational efficiency and results in respiratory chain dysfunction [4]. While there are no FDA-approved drugs that directly bind the MT-TL1 RNA, therapeutic strategies include the use of taurine to restore tRNA modification and L-arginine to treat the vascular complications of MELAS [4, 5]. Advanced experimental approaches are also investigating the use of mitochondrial-targeted nucleases, such as TALENs or ZFNs, to selectively eliminate mutant mtDNA and shift heteroplasmy levels toward the wild-type [6].

Other names

TRNL1MTTRL1tRNA-Leu(UUR)Mitochondrial tRNA leucine 1tRNA leucine 1

Restoration of tRNA wobble base modification, reduction of mutant mitochondrial DNA heteroplasmy, and nitric oxide precursor supplementation to alleviate metabolic and vascular dysfunction.