Volume 18 Issue 2, February 2022

Optogenetic and thermogenetic tools have been limited to applications for single-state control of cellular processes. A single-component optogenetic tool was found to act as both a temperature sensor and a photoreceptor, enabling multi-state control of developmental signaling.

To avoid strife at the interface of basic carbon and nitrogen metabolism, Bacillus subtilis has developed a rather combative solution. If needed, its glutamate synthase suppresses conflicting glutamate breakdown by directly binding and immobilizing its metabolic opponent, glutamate dehydrogenase.

Reliable quantification and tracing of RNA molecules remain challenging goals. A new fluorescent RNA tag, developed based on a natural adenine-sensing riboswitch and named Squash, offers superior imaging properties and accurate quantification in living cells.

Chimeric antigen receptor T cells (CAR-T cells) are often hindered by the concurrent challenges of variable antigen expression patterns and immunosuppressive tumor microenvironments. A new approach enhances CAR-T cells by coexpressing bacterial enzymes that activate prodrugs in high concentrations at the disease site.

The Review summarized the recent progress in chemical probes and drug candidates for epigenetic writer enzymes and discussed the implication of targeting the chromatin regulatory landscape in cancer biology and therapy.

Nutrient stress induces ATF4 expression via translation reinitiation, which involves eIF3 retainment on the elongating ribosome. This translational reprogramming is mediated by stress-induced removal of the O-GlcNAc modification from eIF3a.

RNA acetyltransferase TmcA functions as a lysine 2-hydroxyisobutyryltransferase to regulate bacterial transcription in response to acid stress in prokaryotes.

The BcLOV4 photoreceptor was used to generate single-component optogenetic signaling probes whose activation dynamics are dependent on light and temperature, allowing multiplexing of blue-light-sensitive tools in mammalian cells

In Bacillus subtilis, glutamate synthase (GltAB) and glutamate dehydrogenase (GudB) catalyze opposite reactions that synthesize and break down glutamate, respectively, and form a regulatory complex to inhibit GudB under glutamate-limited conditions.

Structural characterization and fluorogenic screening of a hydroxylase–halogenase chimera library enable switching of a hydroxylase into a robust and selective halogenase.

The adenine riboswitch was evolved into a fluorogenic aptamer by randomizing the sequence and size of the ligand-binding pocket. The resulting fluorogenic aptamer, Squash, is highly folded and was adapted for ratiometric live imaging of SAM.

Truong et al. report crystal structures of Squash, a fluorophore-activating aptamer RNA evolved from the adenine riboswitch. Squash preserves the overall scaffold of the adenine riboswitch, yet has a highly divergent ligand-binding site.

Engineering of a bacterial-derived retron system enhances production of reverse-transcribed DNA for genome-editing applications in bacteria, yeast and human cells.

A genome-wide CRISPR screen revealed that loss of general control nonderepressible 2 (GCN2) kinase increases cellular resistance to the pan-ErbB inhibitor neratinib with neratinib directly binding and activating GCN2 kinase activity.

The synthetic enzyme-armed killer (SEAKER) approach equips chimeric antigen receptor (CAR)-T cells with the capacity to express enzymes that process anticancer prodrugs at tumor sites of action.

Cryo-EM analysis with DEER spectroscopy and molecular dynamics simulations of the ABC exporter BmrCD reveal dual-mode substrate binding in an ATP- and substrate-bound state.