Epitranscriptomic regulation of insecticide resistance

Abstract

<i>N</i> ⁶-methyladenosine (m⁶A) is the most prevalent messenger RNA modification in eukaryotes and an important posttranscriptional regulator of gene expression. However, the biological roles of m⁶A in most insects remain largely unknown. Here, we show that m⁶A regulates a cytochrome P450 gene (<i>CYP4C64</i>) in the global whitefly pest, <i>Bemisia tabaci</i>, leading to insecticide resistance. Investigation of the regulation of <i>CYP4C64</i>, which confers resistance to the insecticide thiamethoxam, revealed a mutation in the 5' untranslated region of this gene in resistant <i>B. tabaci</i> strains that introduces a predicted m⁶A site. We provide several lines of evidence that mRNA methylation of the adenine at this position, in combination with modified expression of m⁶A writers, acts to increase expression of <i>CYP4C64</i> and resistance. Collectively, these results provide an example of the epitranscriptomic regulation of the xenobiotic response in insects and implicate the m⁶A regulatory axis in the development of insecticide resistance.