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== Translational readthrough == '''Stop codon suppression''' or '''translational readthrough''' occurs when in translation a stop codon is interpreted as a sense codon, that is, when a (standard) amino acid is 'encoded' by the stop codon. Mutated [[tRNA]]s can be the cause of readthrough, but also certain [[nucleotide]] motifs close to the stop codon. Translational readthrough is very common in viruses and bacteria, and has also been found as a gene regulatory principle in humans, yeasts, bacteria and drosophila.<ref name="pmid14759362">{{cite journal |vauthors=Namy O, Rousset JP, Napthine S, Brierley I |title=Reprogrammed genetic decoding in cellular gene expression |journal=Molecular Cell |volume=13 |issue=2 |pages=157–68 |year=2004 |pmid=14759362 |doi=10.1016/S1097-2765(04)00031-0 |doi-access=free }}</ref><ref name="pmid25247702">{{cite journal | vauthors = Schueren F, Lingner T, George R, Hofhuis J, Gartner J, Thoms S | title = Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals | journal = eLife | volume = 3 | pages = e03640 | date = 2014 | pmid = 25247702 | doi = 10.7554/eLife.03640 | pmc=4359377 | doi-access = free }}</ref> This kind of endogenous translational readthrough constitutes a variation of the [[genetic code]], because a stop codon codes for an amino acid. In the case of human [[malate dehydrogenase]], the stop codon is read through with a frequency of about 4%.<ref name="pmid27881739">{{cite journal | vauthors = Hofhuis J, Schueren F, Nötzel C, Lingner T, Gärtner J, Jahn O, Thoms S | title = The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code | journal = Open Biol | volume = 6 | issue = 11 | pages = 160246 | date = 2016 | pmid = 27881739 | doi = 10.1098/rsob.160246 | pmc=5133446}}</ref> The amino acid inserted at the stop codon depends on the identity of the stop codon itself: Gln, Tyr, and Lys have been found for the UAA and UAG codons, while Cys, Trp, and Arg for the UGA codon have been identified by mass spectrometry.<ref name="pmid25056309">{{cite journal |vauthors=Blanchet S, Cornu D, Argentini M, Namy O |title=New insights into the incorporation of natural suppressor tRNAs at stop codons in ''Saccharomyces cerevisiae''. |journal=Nucleic Acids Res. |volume=42 |issue=15 |pages=10061–72 |year=2014 |pmid=25056309 |doi=10.1093/nar/gku663 |pmc=4150775}}</ref> Extent of readthrough in mammals have widely variable extents, and can broadly diversify the proteome and affect cancer progression.<ref>{{cite journal |last1=Ghosh |first1=Souvik |last2=Guimaraes |first2=Joao C |last3=Lanzafame |first3=Manuela |last4=Schmidt |first4=Alexander |last5=Syed |first5=Afzal Pasha |last6=Dimitriades |first6=Beatrice |last7=Börsch |first7=Anastasiya |last8=Ghosh |first8=Shreemoyee |last9=Mittal |first9=Nitish |last10=Montavon |first10=Thomas |last11=Correia |first11=Ana Luisa |last12=Danner |first12=Johannes |last13=Meister |first13=Gunter |last14=Terracciano |first14=Luigi M |last15=Pfeffer |first15=Sébastien |last16=Piscuoglio |first16=Salvatore |last17=Zavolan |first17=Mihaela |title=Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation |journal=The EMBO Journal |date=15 September 2020 |volume=39 |issue=18 |pages=e103922 |doi=10.15252/embj.2019103922|pmid=32812257 |pmc=7507497 }}</ref>
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