ICT1 comes to the rescue of mitochondrial ribosomes.

In the current issue, Richter et al (2010) show that mammalian mitochondrial ribosomes contain a ribosomal protein (ICT1) that acts as a ribosome-dependent, codonindependent peptidyl-tRNA hydrolase. This ribosomal protein can rescue ribosomes stalled on mRNAs lacking a termination codon. Every translational system runs into trouble when it encounters mRNAs that have lost the translation termination codon (Akimitsu, 2008). Different translational systems have responded to the challenge of non-stop mRNAs with different strategies. Bacteria use a trans-translation mechanism in which tmRNA enters the A-site of a ribosome stalled at the 30 end of mRNA. One region of this RNA donates Ala to the stalled polypeptide chain (Figure 1A). The other portion acts as mRNA, displacing the non-stop RNA and providing information for a short peptide tail and a conventional stop codon. In the eukaryotic cytoplasm, a ribosome stalled at the poly(A) tail of the non-stop mRNA is recognized by a protein such as yeast Ski7p (Figure 1B). The mRNA is then degraded. The stalled ribosome:non-stop mRNA complexes are also translationally repressed. Animal cells have a distinct protein biosynthetic system in the mitochondria, which is responsible for the synthesis of essential polypeptides that are subunits of the respiratory chain complexes. In a fascinating analysis described in this issue (Richter et al, 2010), mammalian mitochondrial ribosomes are shown to handle the problem of non-stop mRNAs by a unique mechanism (Figure 1C). These ribosomes have a novel protein, ICT1, which acts as a ribosomedependent codon-independent peptidyl-tRNA hydrolase. When mitochondrial ribosomes stall at the 30 end of a non-stop mRNA, ICT1 cleaves the peptidyl-tRNA, releasing the nascent chain and freeing the ribosomes for proper recycling. ICT1 is one of four members of the release factor family found in mitochondria. It has a number of homologues in bacteria and may be of prokaryotic origin. Richter et al show that immunoprecipitation of ICT1 pulls down many