The fidelity of translation is determined at two major points: the accuracy of aminoacyl-tRNA selection by the ribosomes and synthesis of cognate amino acid/tRNA pairs by aminoacyl-tRNA synthetases (aaRSs) in the course of the aminoacylation reaction. The most important point in aminoacylation is the accurate recognition of cognate substrates coupled with discrimination of
non-cognates. While this is generally accomplished by a single enzyme, we have recently found that discrimination against lysine analogues requires the existence of two unrelated lysyl-tRNA synthetases. For other amino acids, initial recognition is not sufficiently accurate with errors being
corrected by an intrinsic editing activity. Recent studies indicate how editing prevents the misinterpretation of phenylalanine as tyrosine in the genetic code and have shown the importance of this process in vivo. More recent studies indicate that while these editing reactions are critical in
the cytoplasm, some are absent from mitochondria suggesting that the overall fidelity of protein synthesis might be reduced in this compartment.Vjernost translacije bitno ovisi o točnosti dvaju koraka: odabiru aminoacil-tRNA na ribosomu i sintezi ispravnih aminoacil-tRNA pomoću odgovarajućih aminoacil-tRNA-sintetaza u reakciji aminoaciliranja. Najvažniji događaj u aminoaciliranju precizno je prepoznavanje pripadnih supstrata (tRNA i aminokiseline) i diskriminacija nepripadnih. Iako taj posao uglavnom obavlja po jedan enzim za svaki par tRNA : aminokiselina, nedavno smo ustanovili da su za diskriminaciju analoga lizina potrebne dvije različite lizil-tRNA-sintetaze. U nekim drugim slučajevima otkriveno je da su pogreške u odabiru tRNA i njihovih pripadnih aminokiseline i suviše velike, pa je nužan
naknadni popravak pogrešnih produkata u reakciji aminoaciliranja, koji također mogu katalizirati neke aminoacil-tRNA-sintetaze. Na primjeru krivog odabira tirozina umjesto fenilalanina, te naknadnog popravka, pokazano je kako je mogućnost korekcije važna u sprečavanju pogrešne translacije genetičkog koda in vivo. Najnovija istraživanja pokazala su da su mehanizmi popravka od ključne važnosti u citoplazmi, no neki se ne zbivaju u mitohondriju, ukazujući na smanjenu ukupnu točnost biosinteze proteina u ovom staničnom odjeljku
