Kaempfer Raymond
Department of Molecular Virology, The Hebrew University, Hadassah Medical School, 91120 Jerusalem, Israel.
EMBO Rep. 2003 Nov;4(11):1043-7. doi: 10.1038/sj.embor.embor7400005.
RNA-mediated control can evolve far more rapidly than mechanisms that rely on proteins, creating selective advantages in adaptive gene regulation. Recently, evidence has emerged that messenger RNA is a source of cis-acting RNA elements that sense external signals and thereby regulate gene expression. With exquisite specificity, metabolite-sensing riboswitches control the formation or translation of prokaryotic mRNA. In eukaryotes, RNA sensors in human antiviral cytokine genes that encode tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been shown to activate strongly the RNA-dependent protein kinase PKR, a stress kinase that is also activated by double-stranded RNA--a hallmark of viral infection. These cis-acting RNA elements in the TNF-alpha and IFN-gamma transcripts function as sensors of intracellular PKR levels and regulate gene expression at the level of mRNA splicing and translation, respectively. Although RNA sensors in bacteria may be remnants of an ancient RNA world, it is likely that they form an integral part of higher eukaryotic genomes as well.
RNA介导的调控比依赖蛋白质的机制进化得快得多,这在适应性基因调控中创造了选择优势。最近,有证据表明信使RNA是顺式作用RNA元件的来源,这些元件能感知外部信号,从而调控基因表达。代谢物感应核糖开关以极高的特异性控制原核生物mRNA的形成或翻译。在真核生物中,人类抗病毒细胞因子基因中的RNA传感器,这些基因编码肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ),已被证明能强烈激活RNA依赖性蛋白激酶PKR,一种应激激酶,它也能被双链RNA激活,而双链RNA是病毒感染的标志。TNF-α和IFN-γ转录本中的这些顺式作用RNA元件分别作为细胞内PKR水平的传感器,在mRNA剪接和翻译水平上调控基因表达。尽管细菌中的RNA传感器可能是古老RNA世界的残余,但它们很可能也是高等真核生物基因组的一个组成部分。