Volume 15 Issue 11, November 2019

The growth and guidance of axons dictate their trajectories and are critical for neural-circuit formation. Research in this issue uncovers a new mechanism for regulation of axon growth and guidance that acts via extracellular phosphorylation of a receptor.

Riboswitches enable microbes to rapidly respond to changing levels of metabolites. A high-throughput platform reveals how RNA structural transitions kinetically compete during transcription in a new mechanism for riboswitch function.

Cytoplasmic dynein is a complex molecular motor that steps along microtubules. Advanced biophysical measurements reveal a surprising role for the dynein tail domain in the allosteric control of dynein’s mechanochemistry within assemblies composed of multiple dynein motors.

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 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.

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 phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell survival.

The authors characterize the cotranscriptional folding of the Clostridium beijerinckii pfl ZTP riboswitch in response to its ligand ZMP, and reveal that an internal RNA strand displacement and riboswitch sequence play important roles in the process.

Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles, respectively.

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.

Single-molecule analysis revealed that the velocity and force generation of the mammalian dynein–dynactin complex is regulated by activating adaptors and tail–tail interactions between two dyneins.

Synthetic microbial consortia were applied to demonstrate that oscillatory gene expression in a bacterial population can be propagated over longer distances by activating a localized positive feedback loop.

A light-activated RNA labeling method was developed to determine spatial organization of a transcriptome and found that ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial membrane.

Ancestral protein reconstruction followed by biochemical and structural analyses characterizes the evolutionary trajectory of methyl-parathion hydrolase from an ancestral dihydrocoumarin hydrolase through the accumulation of five key mutations.