But how does readthrough reinterpret the genetic code?
Functional translational readthough involves recoding, that is the genetic code is interpreted other than normal. Understandably, in humans this is a rare thing. But lactate and malate dehydrogenase do it. These two enzymes, more precisely: the mRNAs encoding these two enzymes like their endogenous stop codon being over-read (2% and 4%, respectively) and a little peptide extension added to its normal C-terminus. These extensions carry peroxisome targeting signals, but this is another story. The question here is: How does readthrough re-interpret the genetic code? Using mass spec, we, well Olaf Jahn from the Max-Planck-Institute for Experimental Medicine in Göttingen have/has been able to identify the amino acids that are inserted in place of the stop codon: tryptophan and arginine. While this may not be surprising, given that these amino acids, together with cysteine, are linked to near-cognate tRNAs, identifying those, has been a formidable challenge, and it is the first time, that endogenous readthrough-amino acids have been identified in humans!