GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289861/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289861GEOGSEfalseGlobal and specific mechanisms stimulate mistranslation in cancerTryptophan codon-specific mistranslation, in the form of ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignments (substitutants), is induced in cancer cells by the limiting level of tryptophan imposed by anti-tumor immunity. While frameshifting is driven by the oncogenic MAPK pathway, whether substitutants are genetically regulated is unknown. Here, we screened for genetic mechanisms that control W>F substitutants following IFNγ-mediated tryptophan shortage. This screen identified ADAR1, an enzyme that converts adenosine to inosine in double-stranded RNA molecules, and FTSJ1, an enzyme that 2’-O-methylates the anticodon region of several tRNAs. We demonstrate that ADAR1 sustains the expression of key players of the ribosome quality control pathway, which in turn is essential for mistranslation events. FTSJ1, in contrast, specifically drives W>F mistranslation by methylation of tRNATrp to promote its binding to WARS1 loaded with phenylalanine instead of tryptophan. As both ADAR1 and FTSJ1 levels are elevated in many cancer types, we propose that cancer cells deploy global and specific mechanisms to stimulate mistranslation in response to anti-tumor immunity.2026/08/26GSE289861GSM8800467GSM8800468GSM880046921697289861Homo sapiens