Institute of Cell Biology and Neuroscience, Goethe University Frankfurt, Max-von-Laue-Strasse 13, D-60438 Frankfurt am Main, Germany.
Institute of Biochemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, D-35392 Giessen, Germany.
J Mol Cell Biol. 2019 Oct 25;11(10):930-939. doi: 10.1093/jmcb/mjz043.
RNA-binding proteins (RBPs) are key regulators in post-transcriptional control of gene expression. Mutations that alter their activity or abundance have been implicated in numerous diseases such as neurodegenerative disorders and various types of cancer. This highlights the importance of RBP proteostasis and the necessity to tightly control the expression levels and activities of RBPs. In many cases, RBPs engage in an auto-regulatory feedback by directly binding to and influencing the fate of their own mRNAs, exerting control over their own expression. For this feedback control, RBPs employ a variety of mechanisms operating at all levels of post-transcriptional regulation of gene expression. Here we review RBP-mediated autogenous feedback regulation that either serves to maintain protein abundance within a physiological range (by negative feedback) or generates binary, genetic on/off switches important for e.g. cell fate decisions (by positive feedback).
RNA 结合蛋白(RBPs)是基因表达转录后调控的关键调节因子。其活性或丰度的改变与许多疾病有关,如神经退行性疾病和各种类型的癌症。这凸显了 RBP 蛋白稳态的重要性以及严格控制 RBPs 表达水平和活性的必要性。在许多情况下,RBPs 通过直接结合并影响自身 mRNA 的命运来进行自我调控的反馈,从而对自身的表达进行控制。对于这种反馈控制,RBPs 采用了多种机制,这些机制在基因表达的转录后调控的各个层面上发挥作用。在这里,我们回顾了 RBP 介导的自体反馈调节,它既可以维持蛋白质丰度在生理范围内(通过负反馈),也可以产生二进制的、遗传的开/关开关,这些开关对于例如细胞命运决定(通过正反馈)非常重要。