Epitranscriptomic regulation of insecticide resistance

Abstract

N6-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 (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 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 CYP4C64 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.

Point Mutations in FgSdhC2 or in the 5′ Untranslated Region of FgSdhC1 Confer Resistance to a Novel Succinate Dehydrogenase Inhibitor Flubeneteram in Fusarium graminearum

“…This mutation introduces a predicted m 6A site, and methylation of the adenine at this position acts to increase the expression of CYP4C64 in B. tabaci under thiamethoxam-untreated or -treated conditions . However, compared with the WT strain, the point mutation (−57 bp A to T) in the 5′UTR of FgSdhC 1 did not change the constitutive expression of FgSdhC 1 under Flu-untreated conditions but significantly reduced the expression of FgSdhC 1 under Flu-treated conditions.…”

Transcriptional expression of m6A and m5C RNA methyltransferase genes in the brain and fat body of honey bee adult workers

“…Epigenomic marks are associated with modulation of the expression of pesticide resistant genes in the beetle Meligethes aeneus ( Erban et al, 2017 ). Also, strong evidence suggests that the expression of METTL3, METTL14 and a set of detoxification P450 genes along with increased levels of m 6 A marks confer thiamethoxam resistance to a strain of whitefly crop pest, Bemisia tabaci ( Yang et al, 2021 ). It is important to consider that pollen is a common source of pesticides in agricultural sites and the contamination can be the cause of poisoning incidents of honey bees ( Kiljanek et al, 2016 ).…”

Regulation of GSTu1-mediated insecticide resistance in Plutella xylostella by miRNA and lncRNA

“…A series of trans-and cis-regulatory elements have been identified to mediate detoxification gene expression in insecticide-resistant insects, especially transcription factors [54,55] and miRNAs [33,34]. Methylation of mRNA was recently confirmed to be responsible for the regulation of the expression of the cytochrome P450 gene (CYP4C64), which in turn is responsible for insecticide resistance in the global whitefly pest Bemisia tabaci [56]. However, very few studies have strongly revealed the functions of lncRNAs in the regulation of resistance-associated genes.…”