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Abstract：
Juvenile hormone (JH) is an indispensable insect hormone that is critical in regulating insect development and physiology. N6-methyladenosine (m6A) is the most abundant modification of RNA that regulates RNA fate in eukaryotic organisms. However, the relationship between m6A and JH remains largely unknown. Here, we found that the application of a Juvenile hormone analog (JHA) extended the larval period of Bombyx mori and increased the weight and thickness of the cocoon. Interestingly, global transcriptional patterns revealed that m6A-related genes are specifically regulated by JHA in the posterior silk gland (PSG) that synthesizes the major component of cocoon silk. By transcriptome and m6A sequencing data conjointly, we discovered that JHA significantly regulated the m6A modification in the PSG of B. mori and many m6A-containing genes are related to nucleic acid binding, nucleus, and nucleobase-containing compound metabolism. Notably, 547 genes were significantly regulated by JHA at both the m6A modification and expression levels, especially 16 silk-associated genes, including sericin2, seroin1, Serine protease inhibitors 4 (BmSPI4), Serine protease inhibitors 5 (BmSPI5), and LIM domain-binding protein 2 (Ldb). Among them, 11 silk associated genes were significantly affected by METTL3 knockdown, validating that these genes are targets of m6A modification. Furthermore, we confirm that JHA directly regulates the expression of BmSPI4 and BmSPI5 through m6A modification of CDS regions. These results demonstrate the essential role of m6A methylation regulated by JH in PSG, and elucidate a novel mechanism by which JH affects silk gland development via m6A methylation. This study uncovers that m6A modification is a critical factor mediating the effect of JH in insects.
摘要：
幼体激素（JH）是一种不可或缺的昆虫激素，对调节昆虫发育和生理至关重要。N6-甲基腺苷（m6A）是调节真核生物中RNA命运的最丰富的RNA修饰。然而,M6A和JH之间的关系在很大程度上仍然未知。这里,我们发现，使用少年激素类似物（JHA）延长了Bombyxmori的幼虫期，并增加了茧的重量和厚度。有趣的是,全局转录模式显示，m6A相关基因在合成茧丝主要成分的后丝腺（PSG）中受到JHA的特异性调控。通过转录组和m6A测序数据的联合，我们发现JHA显著调节了M.m6A的修饰，许多含有m6A的基因与核酸结合有关，核，和含核碱基的化合物代谢。值得注意的是,547个基因在m6A修饰和表达水平均受到JHA的显著调控,特别是16个丝相关基因，包括sericin2，seroin1，丝氨酸蛋白酶抑制剂4（BmSPI4），丝氨酸蛋白酶抑制剂5（BmSPI5），和LIM结构域结合蛋白2(Ldb)。其中,11个丝相关基因受到METTL3敲低的显著影响，验证这些基因是m6A修饰的靶标。此外，我们证实JHA通过CDS区的m6A修饰直接调节BmSPI4和BmSPI5的表达。这些结果证明了由JH调节的m6A甲基化在PSG中的重要作用，并阐明了JH通过m6A甲基化影响丝腺发育的新机制。这项研究发现m6A修饰是介导JH在昆虫中作用的关键因素。
