2 replies to this topic

[John Schloendorn]

What exactly is wrong with sending nuclear-coded mRNAs to the mitos, rather than proteins?

Although the import pathway in anmials is not known, the addition of a yeast tRNA import factor enabled tRNA import in human cells.[1] This paper would suggest the strategy to tag mRNAs with a suitable aptamer sequence (such as a tRNA) that binds some mitochondrially targeted protein (such as the same yeast import factor) to piggy-back into the mito. We could plausibly get around protein hydrophobicity, codon adaptation, possible saturation of the TIM/TOM complex and a universal vector might be used for all the 13 genes and the tRNAs (which also need to be allotopically expressed if the mito DNA is to be scrambled). I guess this would not be all that hard to test, if only someone had the motivation, would it?

[ag24]

This is certainly a viable strategy in principle, and Tarassov has made great strides in pushing it forward, but it's probably harder than allotopic expression. The main reason for pessimism is that no case of mRNA or ribosomal RNA import (except the 5SRNA) is known in any species at all -- the two main rRNAs are always mt-coded, even in species that have experienced so much pressure to shrink their mtDNA that they have moved every single tRNA gene. There are protein-coding genes for which this is true too of course, but there we know why (simple probabilities when a lot of transmembrane domains need to be softened up simultaneously). With the rRNAs (and mRNAs) there's no real clue to what the problem is.

That said, it's certainly worth trying, and if I had a fifth slot in the relevant SENS2 session then Tarassov would almost certainly have got it. My only real reason for not including him this time is that he hasn't made any real progress since the original work (pubmed 10988073) -- but nor has Lightowlers, so it was a toss-up really.