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Seeing both sides. Human pseudouridine synthase Pus10 was found to have two different functions: one is to install pseudouridine modification in tRNAs in a catalytic activity-dependent manner, and the other is to promote miRNA biogenesis in a catalytic-activity-independent manner. The cover depicts two sides of wings pieced together from the same giant blue morpho butterfly symbolizing the dual function of PUS10.
Chris Dobson passed away on September 8th, leaving a wide-reaching legacy. He is best known for revealing the generality of the phenomenon of protein misfolding and aggregation and has provided inspiration for generations of researchers.
The traditional function of pseudouridine synthases is to convert uridine residues in RNA to pseudouridines. A study reveals a new function for the human PUS10 protein, which enhances micro-RNA maturation in addition to tRNA modification.
Engineered living materials (ELMs) with the qualities of both programmable functionalities and environmental tolerance are rare. 3D printing of bacterial spores into resilient living materials provides a viable route to fabricate ELMs that integrate these material attributes.
The ability to engineer synthetic signaling networks has proven challenging for synthetic biology. A breakthrough design strategy shows that bacterial two-component-system-derived parts can be grafted into mammalian cells to create programmable phosphorylation circuitry.
Genetic screens uncover a bioactivation pathway for Lasonolide A involving enrichment in lipid droplets and cleavage into a cytotoxic, soluble metabolite by a lipid droplet-associated serine hydrolase. These findings identify enzymatically regulated phase partitioning as a drug activation mechanism.
The native stress-tolerant phenotypes of various non-conventional microbes have the potential to enable more efficient bioprocessing for chemical production, addressing certain design challenges encountered when using model production hosts.
3D printing agarose hydrogels embedded with Bacillus subtilis spores produce custom-shaped materials that are resistant to environmental stresses, while the bacteria maintain the ability to germinate on the surface and respond to stimuli.
A photocrosslinking-based nucleosome profiling approach is used to identify a conserved basic motif in the ISWI remodeler SNF2h that anchors it to the acidic patch of nucleosome and enables nucleosome sliding activity.
A potent inhibitor of the MRSA virulence regulator, GraR, reverses methicillin resistance, inhibits biofilm formation, limits bacterial survival in macrophages and attenuates virulence in vitro, synergizing with cationic antimicrobial peptides.
Sulfur-triazole exchange (SuTEx) chemistry is a tunable platform for covalent chemoproteomic probes that selectively target tyrosines, used to identify residues with enhanced nucleophilicity and monitor activation of phosphotyrosine sites.
PUS10 exhibits two different functions: one is to promote miRNA biogenesis in a catalytically independent manner; the other is to install pseudouridine modification in tRNAs in a catalytically dependent manner.
A chemoproteomics and protein engineering strategy to investigate metabolic activity of lipid kinases led to assignment of a key role for atypical C1 domains in directing fatty acyl specificity of diacylglycerol kinase function in live cells.
Bacterial two-component signaling machinery has been reprogrammed for orthogonal signaling in mammalian cells that is triggered by small-molecule-mediated dimerization or ligand-induced GPCR/β-arrestin signaling.
A series of positive allosteric modulators of NMDA receptors that can increase agonist potency, increase channel-open probability, and slow receptor deactivation can also decrease single-channel conductance and decrease calcium permeability.
A combinatorial engineering strategy encompassing pathway regulation, heterologous enzymes and subcellular trafficking enables repurposing of the phospholipid biosynthetic pathway in Saccharomyces cerevisiae for the production of oleoylethanolamide.
Lasonolide A is hydrolyzed into a cytotoxic metabolite by a lipid droplet-associated orphan serine hydrolase, showing that lipid droplets can promote drug toxicity by both accumulating and metabolizing drugs in cells.
A hydrophobic tagging method is used to develop a selective degrader for the chromatin regulator EZH2, which inhibits proliferation of triple-negative breast cancer cell lines in vitro and in vivo.