HMRF1L is a human mitochondrial translation release factor involved in the decoding of the termination codons UAA and UAG.

While all essential mammalian mitochondrial factors involved in the initiation and elongation phases of translation have been cloned and well characterized, little is known about the factors involved in the termination process. In the present work, we report the functional analysis of human mitochondrial translation release factors (RF). Here, we show that HMRF1, which had been previously denoted as a human mitochondrial RF, was inactive in in vitro translation system, although it is a mitochondrial protein. Instead, we identified another human mitochondrial RF candidate, HMRF1L, and demonstrated that HMRF1L is indeed a mitochondrial protein that functions specifically as an RF for the decoding of mitochondrial UAA and UAG termination codons in vitro. The identification of the functional mitochondrial RF brings us much closer to a detailed understanding of the translational termination process in mammalian mitochondria as well as to the unraveling of the molecular mechanism of diseases caused by the dys-regulation of translational termination in human mitochondria.

The human mitochondrial translation release factor HMRF1L is methylated in the GGQ motif by the methyltransferase HMPrmC.

We have recently identified the human mitochondrial release factor, HMRF1L, which is responsible for decoding of UAA/UAG termination codons. Here, we identified human mitochondrial methyltransferase, HMPrmC, which methylates the glutamine residue in the GGQ tripeptide motif of HMRF1L. We demonstrate that HMPrmC is targeted to mitochondria and the glutamine residue in the GGQ motif of HMRF1L is methylated in vivo. HMPrmC depletion in HeLa cells leads to decreased mitochondrial translation activity in the presence of the translation fidelity antibiotic streptomycin in galactose containing medium. These results suggest that the methylation of HMRF1L by HMPrmC in human mitochondria is involved in the control of the translation termination process, probably by preventing the undesired suppression of termination codons and/or abortive termination events at sense codons under such conditions, as observed in prokaryotes and eukaryotes systems.