Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism

Intermediary metabolism studies have typically concentrated on four major regulatory mechanisms-substrate availability, allosteric enzyme regulation, post-translational enzyme modification, and regulated enzyme synthesis. Although transcriptional control has been a big focus, it is becoming increasingly evident that many post-transcriptional events are deeply embedded within the core regulatory circuits of enzyme synthesis/breakdown that maintain metabolic homeostasis. The prominent post-transcriptional mechanisms affecting intermediary metabolism include alternative pre-mRNA processing, mRNA stability and translation control, and the more recently discovered regulation by noncoding RNAs. In this review, we discuss the latest advances in our understanding of these diverse mechanisms at the cell-, tissue- and organismal-level. We also highlight the dynamics, complexity and non-linear nature of their regulatory roles in metabolic decision making, and deliberate some of the outstanding questions and challenges in this rapidly expanding field.