RNA m6A demethylase ALKBH4 governs whitefly development

Yang, J.; Wang, C.; Gong, P.; He, C.; Fu, B.; Liu, S.; Wei, X.; Yin, C.; Huang, M.; Du, T.; Liang, J.; Zhou, X.; Nauen, R.; Zhang, Y.; Bass, C.; Yang, X.

doi:10.64898/2026.08.08.743705

bioRxiv · 10.64898/2026.08.08.743705

RNA m6A demethylase ALKBH4 governs whitefly development

Yang, J.·Wang, C.·Gong, P.·He, C.·Fu, B.·Liu, S.·Wei, X.·Yin, C.·Huang, M.·Du, T.·Liang, J.·Zhou, X.·Nauen, R.·Zhang, Y.·Bass, C.·Yang, X.

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Abstract

N6-methyladenosine (m6A) 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 m6A methylases have been partially elucidated in insects, the identity of m6A 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 m6A demethylase in the whitefly, Bemisia tabaci, catalyzing the oxidative reversal of mRNA m6A modifications both in vitro and in vivo. Furthermore, we established that ALKBH4, in coordination with other core components of the m6A 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 m6A modification system, and reveal a conserved yet insect-specific epitranscriptomic regulatory mechanism governing fundamental physiological processes and adaptive phenotypes. Significance statementThe addition of a methyl group to the N6-position of adenosine (m6A) is a highly abundant chemical modification of RNA. However, the functional role of m6A 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 m6A 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 m6A pathway, plays an important role in whitefly development. These findings provide new insight into m6A methylation system of insect.

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Yang, J., Wang, C., Gong, P., He, C., Fu, B., Liu, S., Wei, X., Yin, C., Huang, M., Du, T., Liang, J., Zhou, X., Nauen, R., Zhang, Y., Bass, C., Yang, X.. 2026-08-10. RNA m6A demethylase ALKBH4 governs whitefly development. https://doi.org/10.64898/2026.08.08.743705

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