Towards understanding mRNA-binding protein specificity: lessons from post-transcriptional regulation of ATG mRNA during nitrogen starvation-induced autophagy

Abstract

In this report, we discuss recent discoveries concerning the effects and specificity of different RNA-binding proteins (RBPs) as they pertain to macroautophagy/autophagy. Autophagy is a fundamental cellular degradation and recycling pathway, which has attracted substantial attention because defects in this process are associated with a wide range of human disorders including cancer, neurodegeneration, and metabolic diseases. Autophagy must be tightly controlled—either too much or too little can be deleterious. Therefore, understanding the complex regulation of autophagy is critical to achieve the goal of modulating the process for therapeutic purposes. Autophagy occurs constitutively, but is upregulated in response to stress. Here, we highlight a role for various RBPs in regulating particular autophagy-related (ATG) mRNAs. We briefly summarize recent publications, which focus on the RBPs Dhh1, Pat1, Lsm1–Lsm7 and Dcp2 in the post-transcriptional regulation of certain mRNAs that encode key components of the autophagy machinery. Finally, we consider how the established role of these and other RBPs in enhancing decapping and downregulating mRNAs is not their only function when it comes to regulating stress-related transcripts. Most ATG genes are downregulated during growth, in contrast to the vast majority of the genome; we discuss how certain regulatory factors play a key role in maintaining autophagy at a basal level during growth, while allowing for a rapid increase when cells encounter various stress conditions.