RNA-binding proteins (RBPs) have emerged as key regulators of diverse physiological and metabolic processes in cells. Notably, many metabolic enzymes exhibit moonlighting RNA-binding functions, and a substantial fraction localize to chloroplasts, the primary hub of photosynthesis and cellular metabolic homeostasis. Since chloroplasts originated from free-living cyanobacteria, understanding the RBP repertoire in these ancient phototrophs holds particular evolutionary and functional significance. A comprehensive characterization of the cyanobacterial RBPome is still lacking. Here, we employed Synechococcus elongatus PCC 7942, a model cyanobacterium, to define its RBPome using an RNA-interactome capture approach. We identified 136 RBPs, of which nearly 30% are associated with metabolic pathways, a proportion notably higher than that observed in bacteria, algae, plants, flies, worms, or animals. Strikingly, several enzymes from core metabolic pathways, including glycolysis/gluconeogenesis, the TCA cycle, and the pentose phosphate pathway, that are known RNA binders in humans are also conserved as RBPs in cyanobacteria. We identified a wide array of proteins from the photosynthetic apparatus exhibiting RNA-binding activity, many of which are conserved across the green lineage. In silico structural alignments of RNA-binding metabolic enzymes with their NAD(P)-binding pockets, a potential site for RNA-binding, suggests a broad conservation of RNA-binding capacity of core metabolic enzymes across species. Recent discoveries have revealed that RNA-binding can modulate enzymatic activity. In this context, our findings suggest that RNA-mediated control of core cellular metabolic processes may be widespread in cyanobacteria and riboregulation might be an evolutionarily ancient mechanism, potentially tracing its origins back to cyanobacteria.
Anudarsh et al. (Mon,) studied this question.