Reviews & Analysis

The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) is post-translationally modified during gene expression. A recent study has identified a CTD kinase, Hrr25, that regulates the termination of noncoding RNA genes by recruiting Rtt103, a key termination factor.

Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of E2s.

Phase separation underlies the formation of cellular membrane-less organelles. A new report identifies deacetylation at lysine residues of intrinsically disordered protein regions to drive liquid droplet formation in vitro and stress granule maturation inside cells.

Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug discovery.

Terpenoids are assembled from five-carbon (C5) units, which limits the available scaffold chemical space for the discovery of bioactive molecules. A combination of enzyme and metabolic engineering now enables biosynthesis of a plethora of non-natural C11 terpenoids.

Scientists have combined functional and computational analysis to predict the substrate specificity of a family of glycosyltransferases from Arabidopsis thaliana, creating a tool that enables researchers to classify the donor and acceptor specificity of glycosyltransferase enzymes.

The proteome-wide application of a probe that selectively labels cysteine residues oxidized to the sulfinic acid form reveals the mammalian S-sulfinylome and uncovers novel substrates of the sulfinyl reductase sulfiredoxin, opening yet unexplored realms of cysteine-based redox regulation.

Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and selectivity.

A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific chaperones.

The prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia studies.

One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound complex.

Duramycin is a small post-translationally modified peptide with antibody-like affinity for phosphatidylethanolamine. As it turns out, the same functionality that is essential for duramycin activity helps to catalyze the formation of its conformationally constrained and compact polycyclic architecture.

T cell cross-reactivity enables the immune system to recognize a large array of peptides. A new study shows that T cells can achieve cross-recognition by using the remarkable plasticity of peptides, through flipping the peptide out of the binding cleft.

The design of spiraling cross-α amyloid-like structures reveals fascinating supermolecular fibrils of diverse compactness and stability. The small sequence variations governing cross-α self-assembly properties concur with amyloids being basic building blocks of life and natural targets for microbial structural mimicry.

A computational design approach was used to develop a genetically encoded FRET-based optical sensor that is aimed at monitoring extracellular glycine levels in brain tissue with the sensitivity and resolution to discern differences in dendritic spine and shaft environment and concentration dynamics upon afferent stimulation.

Monitoring MHC-I dynamics upon binding to its chaperone TAPBPR helps us understand how optimal peptide sequences are selected for presentation and coordinated with release of the chaperone from the ternary peptide–MHC-I–TAPBPR complex.

Calcium channels are crucial regulators of a broad range of biological processes. A photoswitchable chemical probe allows the opening and closing of these channels with unprecedented temporal resolution, providing new opportunities to study calcium-dependent signaling pathways in real time.

Synthetic biology is enabling functional metagenomics by providing genetic circuits to identify new pathways that, in turn, facilitate design of new biosensors and synthetic systems.

Establishment of the germ cell lineage requires post-transcriptional regulation of mRNAs, yet the underlying molecular mechanisms are not fully understood in vertebrates. A small-molecule inhibitor of germ cell formation reveals a noncanonical translation system used in zebrafish embryos.

Adaptive survival signaling can promote resistance to individual kinase inhibitors. A new study used a pathway-based approach to characterize shared kinome-wide rewiring mechanisms across multiple kinase inhibitors and developed rational drug-combination approaches that target cross-talk between two signaling pathways.