Screening of Drosophila melanogaster RNA m6A modification pathway factors
Received date: 2024-12-03
Revised date: 2025-01-25
Online published: 2025-03-03
Supported by
National Natural Science Foundation of China(31970786);National Natural Science Foundation of China(32270868)
N6-methyladenosine (m6A), one of the most prevalent mRNA modifications, plays crucial roles during animal and plant development and in various physiological and pathological processes. Previous studies have characterized m6A methyltransferase complexes, demethylases, and m6A-binding proteins, but as a relatively new epitranscriptomic pathway, it is likely that new m6A components remain to be discovered. To explore the effects of m6A modification on tissues and organs, the m6A reader Ythdc1 was overexpressed in Drosophila melanogaster eye imaginal discs. Our results showed that overexpression of Ythdc1 leads to ectopic expression of Sxl in males, the rough eye in both males and females, and the activation of JNK signaling and apoptotic pathway. In order to screen m6A modifiers using the rough eye phenotype, a stable Drosophila strain overexpressing Ythdc1 was further constructed. By screening of more than 1,500 RNAi lines, several repressors and enhancers that may be involved in m6A modification were successfully identified. These genes are less studied in m6A pathway, and therefore we further verified them and conducted preliminary mechanistic analyses on them. In summary, this study identified multiple potential factors of the m6A modification pathway, expanded our understanding of the m6A modification network, and provided ideas and directions for exploring new regulatory mechanisms of this important pathway.
Key words： Drosophila melanogaster; m6A; Ythdc1; Sxl; modifier screen
Shuyang Gao, Houguang Lu, Yanhua Wang, Dong Yan . Screening of Drosophila melanogaster RNA m6A modification pathway factors[J]. Hereditas(Beijing), 2025 , 47(4) : 476 -488 . DOI: 10.16288/j.yczz.24-341
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