miRNA let-7 expression is regulated by glucose and TNF-α by a remote upstream promoter

miRNA let-7 expression is regulated by glucose and TNF-α by a remote upstream promoter
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DOI:
10.1042/bj20150224
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发表时间:
2015-12-01
影响因子:
4.1
通讯作者:
Krook, Anna
Krook, Anna
中科院分区:
生物学3区
文献类型:
--
作者:
Katayama, Mutsumi;Sjogren, Rasmus J. O.;Krook, Anna

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miRNA调节蛋白质丰度并控制代谢疾病(如肥胖症和2型糖尿病(T2 D))中细胞过程和生物功能的各个方面。Let-7(致命)miRNA特异性靶向与T2 D相关的基因,并参与外周葡萄糖代谢的调节,但let-7 miRNA表达的直接调节因子尚不清楚。在本研究中,我们报告了一个假定的启动子区域的let-7a-1,let-7 f-1和let-7 d基因簇的9号染色体上,并表征这个新的区域的启动子活性。我们发现,启动子活性和let-7 miRNA表达动态调节不同的因素,包括血清,葡萄糖,肿瘤坏死因子(TNF)-α和咖啡因。这些发现将有助于理解精确的启动子元件之间的相互作用,以控制let-7 miRNA基因的转录和翻译。
miRNAs regulate protein abundance and control diverse aspects of cellular processes and biological functions in metabolic diseases, such as obesity and type 2 diabetes (T2D). Let (lethal)-7 miRNAs specifically targets genes associated with T2D and have been implicated in the regulation of peripheral glucose metabolism, yet the direct regulators of let-7 miRNA expression are unknown. In the present study, we report on a putative promoter region for the let-7a-1, let-7f-1 and let-7d gene cluster on chromosome 9 and characterize the promoter activity of this novel area. We show that promoter activity and let-7 miRNA expression is dynamically regulated in response to different factors including serum, glucose, tumour necrosis factor (TNF)-alpha and caffeine. These findings will contribute to understanding the interaction between precise promoter elements to control the transcription and translation of let-7 miRNA genes.