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Auto-regulatory feedback by RNA-binding proteins
Michaela Müller-McNicoll 1, Oliver Rossbach2, Jingyi Hui3, and Jan Medenbach 4,*
1 Institute of Cell Biology and Neuroscience, Goethe University Frankfurt, Max-von-Laue-Strasse 13, D-60438 Frankfurt am Main, Germany
2 Institute of Biochemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, D-35392 Giessen, Germany
3 State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
4 Institute of Biochemistry I, University of Regensburg, Universitaetsstrasse 31, D-93053 Regensburg, Germany
*Correspondence to:Jan Medenbach, E-mail: Jan.Medenbach@ur.de
J Mol Cell Biol, Volume 11, Issue 10, October 2019, Pages 930-939  https://doi.org/10.1093/jmcb/mjz043
Keyword: autogenous regulation, protein homeostasis, RNA-binding proteins, post-transcriptional regulation of gene expression

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).