RNA m6A methylation suppresses insect juvenile hormone degradation to minimize fitness costs in response to a pathogenic attack
Bioinsecticides and transgenic crops based on the bacterial pathogen Bacillus thuringiensis (Bt) can effectively control diverse agricultural insect pests, nevertheless, insect resistance evolution without causing obvious fitness costs has seriously eroded the sustainable use of these Bt products. Recently, we have discovered that an increased titer of juvenile hormone (JH) favors an insect host (Plutella xylostella) to enhance fitness whilst resisting the Bt pathogen, however, the underlying regulatory mechanisms of the increased JH titer is obscure. Here, we define the involvement of N6-methyladenosine (m6A) RNA modification in modulating the availability of JH in this process. Specifically, we found that two m6A methyltransferase subunit genes, PxMettl3 and PxMettl14, repressed the expression of a key JH-degrading enzyme JH esterase (JHE) to induce an increased JH titer, mitigating the fitness costs associated with a robust defense against the Bt pathogen. This study identifies an as-yet uncharacterized m6A-mediated epigenetic regulator of insect hormones for maintaining fitness during pathogen defense and unveils an emerging Bt resistance-related m6A methylation atlas in insects, which further expands the functional landscape of m6A modification and showcases the pivotal role of epigenetic regulation in host-pathogen interactions. Overall design: To explore the role of m6A modification in the resistance of Plutella xylostella to Bt Cry1Ac, we performed m6A-seq analysis on midgut tissues of Bt Cry1Ac susceptible and resistant strains