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An in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in vivo.
A comprehensive genetic screen reveals new cellular trafficking factors and linker-dependent requirements for antibody–drug conjugate (ADC) cytotoxicity. These new insights may guide the design of optimized ADCs.
A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC recycling.
Via its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon growth.
The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent dioxygenase.
A light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian cells.
An unusual terpene nucleoside, 1-TbAd, made by pathogenic mycobacteria acts as an antacid to block mycobacterial degradation in host cell vacuoles. The antacid activity acts to reduce acidity by neutralizing the pH of these degradative cell organelles.
Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.
Analysis of recent X-ray crystallography data on eukaryotic glycosyltransferases in complex with acceptor and donor substrates reveals structural features that govern substrate specificity and glycosylation site selection.
Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of sepsis.
Asymmetric cell division, which generates daughter cells with distinct characteristics, is a mechanism for creating complex systems through cellular differentiation. Two studies in this issue develop synthetic platforms that program spatial localization of genetic material or signaling molecules to enable asymmetric cell division in Escherichia coli.
The iron chaperone poly(rC)-binding protein 1 (PCBP1) coordinates ferrous iron via its KH3 domain and, together with BolA2 and glutathione, forms a complex that is required for the assembly of [2Fe–2S] clusters on the cytosolic BolA2–Glrx3 chaperone.
Split Cpf1 pairs are identified to enable chemical- and light-induced genome editing via dimerization. Another pair of split Cpf1 can be used to activate gene expression with high efficiency in cells and in mice.
Small molecule or light-inducible gene circuits in Escherichia coli enable asymmetric cell pole localization of diguanylate phosphodiesterase and facilitate asymmetric cell division regulated by c-di-GMP-responsive transcription factors.
The indolmycin biosynthetic pathway in a marine gram-negative bacterium is distinct from its counterpart in terrestrial gram-positive Streptomyces species, using a Streptomyces shunt product as a substrate for an N-demethylindolmycin synthase.
