From Fire and Brimstone: A Retrospective on the Roles of Iron in Bacterial RNA Metabolism

Bacteria must constantly adapt to changing environments, and iron has served as a critical cofactor in essential biochemical processes since life first evolved. Over the years, it has become apparent that iron homeostasis is intricately tangled with RNA metabolism. Diverse proteins and RNAs are sensitive to the levels and redox states of iron, and can trigger various signaling cascades in response to iron starvation, oxidative stress, and other challenges. While it is widely known that iron-binding proteins can serve as environmental sensors, those that also bind to RNA may have far-reaching impacts beyond iron homeostasis. Here, the impact of iron on the metabolism of RNA in bacteria is reviewed, ranging from single-atom cofactors for RNA folding to the widespread post-transcriptional regulatory effects of iron-binding proteins. In this review, the term degradation is used specifically to refer to complete breakdown of an RNA, while the terms processing and maturation refer to an RNA being converted to a shorter, stable, functional form through endonucleolytic and/or exonucleolytic cleavage. We use the term stability to refer to the degradation rate of an RNA. Finally, we consider RNA metabolism an umbrella term encompassing all aspects of RNA synthesis (transcription), post-transcriptional modifications, and processing and degradation by RNases.