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The cover depicts the structures of the RNA aptamers Spinach (green), Mango (orange) and Corn (yellow), which contain G-quadruplexes. Corn provides increased photostability and a red-shifted spectrum that enables imaging of RNA polymerase III transcription, and the structure of Corn reveals an unexpected homodimer. Cover design by Erin Dewalt, based on an image generated by Ethan Tyler. Articles, p1187 and p1195; News & Views, p1140
In contrast to proteins, no intrinsically fluorescent RNA is known to exist in nature. In this issue, a new, red-shifted aptamer–fluorophore complex for RNA imaging that has enhanced photostability is described. The crystal structure of this complex reveals a novel form of RNA small-molecule recognition.
A potent and selective inhibitor of protein SUMOylation, a ubiquitin-like post-translational modification, has been developed, shedding light on the potential for developing new classes of anticancer therapeutics.
Structure-based computational methods have contributed to recent successes in the development of small molecules to study GPCR function and to act as therapeutics, including the identification of new ligands for orphan GPCRs, allosteric regulators, and biased ligands.
A toxic conformation of disease-linked huntingtin protein with expanded polyQ is degraded more slowly than the other conformations, as it is less able to engage the autophagy machinery, explaining its higher toxicity compared to other conformations.
In Pseudoalteromonas rubra, an unclustered biosynthetic gene encodes a di-iron oxygenase-like enzyme that catalyzes regiospecific C–H activation and cyclization of prodigiosin, yet is unrelated to the Rieske oxygenases that produce other cyclized prodiginines.
Engineering of an artificial metabolon complex consisting of an endogenous sugar transporter and a heterologous isomerase couples the uptake of xylose to its downstream reaction, improving ethanol yield and minimizing an undesired side reaction.
An inhibitor of the SUMO-activating (E1) enzyme SAE blocks enzyme activity and total SUMOylation in cells—thereby defining roles for SAE in mitotic progression and chromosome segregation—and also decreases cancer cell proliferation.
Single-molecule FRET microscopy and hidden Markov modeling analysis with the full-length SAM-I riboswitch reveal the existence of multiple conformational states and the effects of Mg2+ and SAM binding on their dynamics and population shifts.
A conserved negative regulator of TORC1, GATOR1, regulates the synthesis of the nitrogen-containing amino acids aspartate and glutamine from the mitochondrial TCA cycle in tune with the amino acid and nitrogen status of cells.
A highly photostable RNA mimic of red fluorescent protein, Corn, was designed and used to image RNA polymerase III transcription. Quantitative imaging of Corn-tagged transcripts revealed transcription dynamics in live cells following mTOR inhibition.
The crystal structure of the fluorogenic RNA aptamer Corn reveals an unexpected homodimer. One molecule of the cognate fluorophore DFHO is encapsulated at the locally asymmetric RNA interface, which is notable for lacking intermolecular base pairs.