School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
Metallomics. 2012 Aug;4(9):928-36. doi: 10.1039/c2mt20065a.
Haem has been previously implicated in the function of the circadian clock, but whether iron homeostasis is integrated with circadian rhythms is unknown. Here we describe an RNA interference (RNAi) screen using clock neurons of Drosophila melanogaster. RNAi is targeted to iron metabolism genes, including those involved in haem biosynthesis and degradation. The results indicate that Ferritin 2 Light Chain Homologue (Fer2LCH) is required for the circadian activity of flies kept in constant darkness. Oscillations of the core components in the molecular clock, PER and TIM, were also disrupted following Fer2LCH silencing. Other genes with a putative function in circadian biology include Transferrin-3, CG1358 (which has homology to the FLVCR haem export protein) and five genes implicated in iron-sulfur cluster biosynthesis: the Drosophila homologues of IscS (CG12264), IscU (CG9836), IscA1 (CG8198), Iba57 (CG8043) and Nubp2 (CG4858). Therefore, Drosophila genes involved in iron metabolism are required for a functional biological clock.
铁元素先前被牵涉到生物钟的功能中,但铁稳态是否与昼夜节律整合在一起尚不清楚。在这里,我们描述了使用黑腹果蝇的生物钟神经元进行的 RNA 干扰 (RNAi) 筛选。RNAi 靶向铁代谢基因,包括参与血红素生物合成和降解的基因。结果表明,Ferritin 2 Light Chain Homologue (Fer2LCH) 是在持续黑暗中保持飞行昼夜活动所必需的。核心分子钟组件 PER 和 TIM 的振荡也在 Fer2LCH 沉默后被打乱。其他具有昼夜生物学潜在功能的基因包括转铁蛋白-3、CG1358(与 FLVCR 血红素输出蛋白具有同源性)和五个与铁硫簇生物合成相关的基因:Drosophila 同源物 IscS (CG12264)、IscU (CG9836)、IscA1 (CG8198)、Iba57 (CG8043) 和 Nubp2 (CG4858)。因此,参与铁代谢的果蝇基因是功能性生物钟所必需的。
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