Ribonuclease-Mediated Control of Body Fat
Ribonuclease-Mediated Control of Body Fat
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DOI：
10.1016/j.devcel.2016.09.018
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发表时间：
2016-11-07
影响因子：
11.8
通讯作者：
Ciosk, Rafal
中科院分区：
文献类型：
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作者：
Habacher, Cornelia;Guo, Yanwu;Ciosk, Rafal
肥胖是一个全球性的健康问题，引起了人们对控制脂肪的分子机制的兴趣。脂肪的转录调控受到了广泛关注，并且参与脂质代谢的关键转录因子，如SBP-1/SREBP，LPD-2/C/EBP和MDT-15，从线虫到哺乳动物都是保守的。然而，人们越来越意识到脂质代谢也可以通过转录后机制来控制。在这里，我们表明，秀丽隐杆线虫RNA酶，REGE-1，相关的MCPIP 1/Zc 3 h12 a/Regnase-1，哺乳动物先天免疫的关键调节，促进体内脂肪的积累。使用外显子-内含子分裂分析，我们发现REGE-1通过降解编码ETS-4（一种脂肪损失促进转录因子）的mRNA来促进脂肪。由于ETS-4反过来诱导rege-1转录，因此REGE-1和ETS-4似乎形成了一个自动调节模块。我们认为，这种类型的脂肪调节可能是至关重要的，如果面对环境的变化，动物必须迅速而精确地重塑其代谢。
Obesity is a global health issue, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention, and key transcription factors involved in lipid metabolism, such as SBP-1/SREBP, LPD-2/C/EBP, and MDT-15, are conserved from nematodes to mammals. However, there is a growing awareness that lipid metabolism can also be controlled by post transcriptional mechanisms. Here, we show that the Caenorhabditis elegans RNase, REGE-1, related to MCPIP1/Zc3h12a/Regnase-1, a key regulator of mammalian innate immunity, promotes accumulation of body fat. Using exon-intron split analysis, we find that REGE-1 promotes fat by degrading the mRNA encoding ETS-4, a fat-loss-promoting transcription factor. Because ETS-4, in turn, induces rege-1 transcription, REGE-1 and ETS-4 appear to form an auto-regulatory module. We propose that this type of fat regulation may be of key importance when, if faced with an environmental change, an animal must rapidly but precisely remodel its metabolism.