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Transcription factor decoys, DNA molecules designed to mimic regulatory DNAs and prevent repressors binding to their DNA targets, are used to achieve de-repression of silent biosynthetic gene clusters, resulting in production of new natural products.
Ten new RNA polymerase II kinases were identified, of these Hrr25 was engineered to enable covalent and noncovalent chemical inhibition in vivo, revealing that this kinase regulates polymerase function at noncoding snoRNA genes.
A NO delivery system that depends on the hydrolysis of an alkyl-galactose-conjugated NO prodrug by an engineered galactosidase developed using a ‘bump-and-hole’ strategy enabled targeted delivery of NO to specific tissues.
Designed split ferredoxins, fused to protein fragments that associate under certain conditions such as the presence of rapamycin, enable transcriptional and post-translational control over electron transfer in Escherichia coli cells and lysates.
A mass-spectrometry-based approach to identify E. coli targets of ppGpp finds 56 putative targets including enzymes involved in nucleotide synthesis, such as PurF, which is directly inhibited by ppGpp, regulating adenosine and guanine nucleotide synthesis.
Structural analysis of the human MePCE methyltransferase domain in complex with 7SK in the presence of SAH or SAM reveals that MePCE has higher affinity for capped 7SK and holds it for subsequent assembly of 7SK RNP.
Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular RNAs.
Protease-cleavable orthogonal-coiled-coil-based (SPOC) systems, in which split viral proteases are activated by small molecules and cleave coiled-coil protease substrates, reprogram signaling with rapid kinetics in mammalian cells.
Structural and biochemical analysis of a UBE2A mutation linked to intellectual disability reveals that the Q93E mutant perturbs the E2 catalytic microenvironment essential for lysine deprotonation during the ubiquitin-transfer process.
ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.
A class of nepetalactol-related short-chain dehydrogenase/reductases (NEPS) captures a reactive enol intermediate produced by iridoid synthase for cyclization and subsequent oxidation into nepetalactones, the active ingredients in catnip.
HDAC6 modulates acetylation at multiple lysine residues in the N-terminal intrinsically disordered region of RNA helicase DDX3X to regulate liquid–liquid phase separation and stress granule maturation.
The combination of multiple fluorophores on a hybridized DNA scaffold enables the development of the reporter cHOClate, which is used to simultaneously and quantitatively image hypochlorous acid (HOCl) and pH during phagosome maturation.
Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor activation.
The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among GPCRs.
Structures of the human thromboxane A2 receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid bilayer.
Co-opting the amyloid machinery from Bacillus subtilis, engineering of TasA fusion proteins enables the assembly of functionalized biofilms with tunable physicochemical properties that are amenable to 3D printing and microencapsulation techniques.
A structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's selectivity.
A directed evolution approach was applied to optimize a set of 12 small-molecule-responsive biosensors, which led to the engineering of “Marionette” strains of Escherichia coli incorporating these sensors for biotechnological applications.
The observation that transcription activator-like effectors (TALES) displace TALES bound at adjacent downstream DNA enables engineered regulation of gene expression, displacement of other DNA binding proteins and construction of logic-gated systems.