Research Group of Glycobiology and Glycotechnology, Mitsubishi-kagaku Institute of Life Sciences, Tokyo, Japan.
PLoS Genet. 2010 Dec 23;6(12):e1001254. doi: 10.1371/journal.pgen.1001254.
Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating α1,3-fucosylation. Further analyses revealed that an RNA-binding protein, second mitotic wave missing (Swm), upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells.
糖基化在多种生物过程中发挥着关键的调节作用，如发育、免疫和神经功能。例如，α1,3-岩藻糖基化是在富含果蝇神经细胞的岩藻糖上添加一个岩藻糖部分，对于神经发育、功能和行为是必不可少的。然而，神经特异性α1,3-岩藻糖基化是如何被调控的，在很大程度上仍然未知。在本研究中，我们使用果蝇 RNAi 文库搜索参与神经特异性蛋白糖基化的基因。我们获得了 109 个影响糖基化的基因，这些基因聚类为九个功能组。其中，RNA 调控组的成员在二次筛选中富集，该筛选鉴定了专门调节α1,3-岩藻糖基化的基因。进一步的分析表明，一种 RNA 结合蛋白，第二次有丝分裂波缺失（Swm），上调了神经特异性糖基转移酶 FucTA 的表达，并促进其 mRNA 从核内输出。这是首次针对糖基化相关基因的大规模遗传筛选，揭示了神经细胞中 fucTA mRNA 的新调控机制。
