RNA m6A Modification Functions in Larval Development and Caste Differentiation in Honeybee (Apis mellifera)

Genetically identical female honeybee larvae with different diets develop into sterile workers or fertile queens. It remains unknown whether the reversible RNA N 6 -methyladenosine (m 6 A) mark functionally impact this "caste differentiation." Here, we profile the transcriptome-wide m 6 A methylome of honeybee queen and worker larvae at three instar stages and discover that m 6 A methylation dynamics are altered by differential feeding. Multiple methylome comparisons show an obvious increase in m 6 A marks during larval development and reveal a negative correlation between gene expression and m 6 A methylation. Notably, we find that worker larvae contain more hypermethylated m 6 A peaks than do queen larvae, and many caste-differentiation-related transcripts are differentially methylated. Chemical suppression of m 6 A methylation in worker larvae by 3-deazaadenosine (DAA) reduces overall m 6 A methylation levels and triggers worker larvae to develop queen caste features. Thus, our study demonstrates that m 6 A functionally impacts caste differentiation and larval development, yet it does not exclude potential contributions from other factors.