RNA m 6 A demethylase ALKBH4 governs whitefly development
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N6-methyladenosine (m 6 A) modification is the most predominant and ubiquitous internal modification of RNA in eukaryotes, serving as a key post-transcriptional regulator of gene expression that is dynamically modulated by methyltransferases (writers) and demethylases (erasers). However, while the functions of m 6 A methylases have been partially elucidated in insects, the identity of m 6 A erasers in arthropods and their chemical catalytic mechanisms, as well as biological functions, remains largely enigmatic. Here, we uncovered 2499 putative methylase genes and 1148 putative demethylase genes in 266 insect genomes, and demonstrated that ALKBH4 functions as an m 6 A demethylase in the whitefly, Bemisia tabaci , catalyzing the oxidative reversal of mRNA m 6 A modifications both in vitro and in vivo. Furthermore, we established that ALKBH4, in coordination with other core components of the m 6 A pathway, fulfills an essential function in regulating the transcript stability of Imaginal Disk Growth Factor 1 (IDGF1) during whitefly development. Collectively, our findings expand the evolutionary scope of the eukaryotic m 6 A modification system, and reveal a conserved yet insect-specific epitranscriptomic regulatory mechanism governing fundamental physiological processes and adaptive phenotypes.
Significance statement
The addition of a methyl group to the N6-position of adenosine (m 6 A) is a highly abundant chemical modification of RNA. However, the functional role of m 6 A in insects and the key enzymes that regulate its levels remains poorly understood. In this study, we explored putative methylase genes and demethylase genes in hundreds insect genomes, and identified an m 6 A RNA demethylase, ALKBH4, in the whitefly, Bemisia tabaci . We demonstrate that ALKBH4 oxidatively reverses mRNA methylation in vivo and in vitro, in combination with other components of the m 6 A pathway, plays an important role in whitefly development. These findings provide new insight into m 6 A methylation system of insect.