National Institute on Aging-Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
Endocrinology. 2010 Apr;151(4):1403-8. doi: 10.1210/en.2009-1123. Epub 2009 Dec 23.
Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3' and 5' untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism.
胰岛素和 IGFs 具有结构相似性,调节包括葡萄糖稳态在内的代谢过程。葡萄糖水平的急性变化会触发胰岛素浓度和胰岛素信号的快速变化。这些过程受到转录后机制的严格调控,这些机制改变了编码胰岛素和胰岛素受体的 mRNAs 的稳定性和翻译。长期的葡萄糖稳态也受到 IGFs 和 IGF 受体的调节,其表达同样受到编码 mRNAs 稳定性和翻译变化的影响。mRNA 半衰期和翻译的控制受 RNA 结合蛋白和 microRNAs 的调控,它们在 3'和 5'非翻译区与靶转录本相互作用。在这篇综述中,我们描述了靶向编码胰岛素、IGFs 及其受体的 mRNAs 的 RNA 结合蛋白和 microRNAs。我们讨论了这些 mRNA 结合因子如何帮助引发胰岛素和 IGF 功能的及时、多样和组织特异性变化,从而对能量代谢进行关键控制。