Genes for iron metabolism influence circadian rhythms in Drosophila melanogaster
Genes for iron metabolism influence circadian rhythms in Drosophila melanogaster
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DOI：
10.1039/c2mt20065a
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发表时间：
2012-01-01
期刊：
影响因子：
3.4
通讯作者：
Missirlis, Fanis
中科院分区：
文献类型：
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作者：
Mandilaras, Konstantinos;Missirlis, Fanis
血红素先前已被牵连在生物钟的功能，但铁稳态是否与昼夜节律整合是未知的。在这里，我们描述了一个RNA干扰（RNAi）的屏幕使用果蝇的时钟神经元。RNAi靶向铁代谢基因，包括那些参与血红素生物合成和降解的基因。结果表明，铁蛋白2轻链同源物（Fer 2LCH）是保持在恒定的黑暗中的苍蝇的昼夜活动所必需的。分子钟中的核心成分PER和TIM的振荡也在Fer 2LCH沉默后被破坏。在昼夜节律生物学中具有推定功能的其他基因包括转铁蛋白-3、CG 1358（其与FLVCR血红素输出蛋白具有同源性）和涉及铁硫簇生物合成的五个基因：果蝇同源物IscS（CG 12264）、IscU（CG 9836）、IscA 1（CG 8198）、Iba 57（CG 8043）和Nubp 2（CG 4858）。因此，果蝇铁代谢相关基因是功能性生物钟所必需的。
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.