Lim D-H, Lee S, Han J Y, Choi M-S, Hong J-S, Lee Y S
College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
Institute of Animal Molecular Biotechnology, Korea University, Seoul, 02841, South Korea.
Insect Mol Biol. 2019 Jun;28(3):444-454. doi: 10.1111/imb.12562. Epub 2019 Jan 18.
Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.
发育生长是一个复杂的过程,涉及多种基因表达的协调调控,而微小RNA(miRNA)在动物发育的各个过程中发挥着关键作用。蜕皮激素响应性miRNA miR-252在果蝇发育的蛹期和成虫期通常会上调。在此,我们发现,在幼虫脂肪体中过表达miR-252会通过减小细胞大小和减少细胞数量来降低组织总质量,从而导致幼虫体型随之减小。此外,miR-252过表达导致幼虫到蛹的转变延迟,前气门外翻存在缺陷,同时成虫的大小和质量也减小。相反,与对照果蝇相比,缺乏miR-252的成年果蝇体重增加。我们发现miR-252直接靶向编码p21激活激酶的mbt,以抑制其表达。值得注意的是,mbt的共过表达挽救了与miR-252过表达相关的发育和生长缺陷,表明mbt是miR-252的一个生物学相关靶点。总体而言,我们的数据支持蜕皮激素/miR-252/mbt调控轴在果蝇发育过程中的生长控制中发挥作用。