The REM phase of gene regulation

‘Classic’ enzymes carry out the housekeeping functions of intermediary metabolism. The past decades have seen a steady trickle of reports of several of these enzymes ‘moonlighting’ as RNA-binding proteins. Although evidence for a physiological role for RNA binding is strong in a few individual examples, no systematic concept has been proposed for the overall phenomenon. We suggest that these diverse observations might herald the existence of currently hidden post-transcriptional regulatory networks between intermediary metabolism and gene expression based on RNA, enzyme and metabolite interactions. We briefly summarize the evidence in support of such networks and discuss how current approaches can be employed for systematic analyses and integration into our understanding of cellular biology, given the technical and conceptual advances of the ‘omics’ age.