Gene Regulation
Do FeS clusters rule bacterial iron regulation?
For decades, the bacterial ferric uptake regulator (Fur) has been thought to respond to ferrous iron to transcriptionally regulate genes required for balancing iron uptake, storage, and utilization. Because iron binding to Fur has never been confirmed in vivo, the physiological iron-sensing mechanism remains an open question. Fontenot et al. now show that Fur purified from Escherichia coli binds an all-Cys-coordinated [2Fe-2S] cluster. This finding opens the exciting possibility that Fur may join numerous well-studied bacterial, fungal, and mammalian proteins that use FeS clusters for cellular iron regulation.Yeast as a detective's assistant: Susan Henry's work on inositol-containing phospholipids
Macromolecules such as proteins, lipids, and carbohydrates often have complex structures that underpin their cellular functions. The sugar alcohol myo-inositol is a notable exception—its simple six-carbon structure is rather unremarkable (Fig. 1) but is used in countless cellular processes in all domains of life (1).Melding the best of two worlds: Cecil Pickett's work on cellular oxidative stress and in drug discovery and development
Many chemicals and cellular processes cause oxidative stress that can damage lipids, proteins, or DNA (1). To quickly sense and respond to this ubiquitous threat, organisms have evolved enzymes that neutralize harmful oxidants such as reactive oxygen species and electrophilic compounds (including xenobiotics and their breakdown products) in cells.Conscious uncoupling of riboswitch functions
Riboswitches alter gene expression in response to ligand binding, coupling sensing and regulatory functions to help bacteria respond to their environment. The structural determinants of ligand binding in the prequeuosine (7-aminomethyl-7-deazaguanine, preQ1) bacterial riboswitches have been studied, but the functional consequences of structural perturbations are less known. A new article combining biophysical and cell-based readouts of 15 mutants of the preQ1-II riboswitch from Lactobacillus rhamnosus demonstrates that ligand binding does not ensure successful gene regulation, providing new insights into these shapeshifting sequences.Glucose regulates MafA transcription factor abundance and insulin gene expression by inhibiting AMP-activated protein kinase in pancreatic β-cells
Insulin mRNA expression in pancreatic islet β-cells is up-regulated by extracellular glucose concentration, but the underlying mechanism remains incompletely understood. MafA is a transcriptional activator specifically enriched in β-cells that binds to the insulin gene promoter. Its expression is transcriptionally and posttranscriptionally regulated by glucose. Moreover, AMP-activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is inhibited by high glucose, and this inhibition is essential for the up-regulation of insulin gene expression and glucose-stimulated insulin secretion (GSIS).
