Epitranscriptomic regulation of insecticide resistance

N(6)-methyladenosine (m(6)A) is the most prevalent messenger RNA modification in eukaryotes and an important posttranscriptional regulator of gene expression. However, the biological roles of m(6)A in most insects remain largely unknown. Here, we show that m(6)A regulates a cytochrome P450 gene (CYP4C64) in the global whitefly pest, Bemisia tabaci, leading to insecticide resistance. Investigation of the regulation of CYP4C64, which confers resistance to the insecticide thiamethoxam, revealed a mutation in the 5′ untranslated region of this gene in resistant B. tabaci strains that introduces a predicted m(6)A site. We provide several lines of evidence that mRNA methylation of the adenine at this position, in combination with modified expression of m(6)A writers, acts to increase expression of CYP4C64 and resistance. Collectively, these results provide an example of the epitranscriptomic regulation of the xenobiotic response in insects and implicate the m(6)A regulatory axis in the development of insecticide resistance.