Volume 13 Issue 1, January 2017

New approaches allow tight control over Cas9 activity using chemical induction. These studies expand the ability to rapidly induce and suppress Cas9-mediated nuclease activity and conditionally modulate the multiplex regulation of endogenous gene expression.

Ferroptosis is characterized by accumulation of lipid peroxidation products and lethal ROS, but the source and identity of lipid death signals that cause toxicity are poorly defined. New studies reveal that ACSL4 controls sensitivity to ferroptosis and that oxidized phosphatidylethanolamines are critical for ferroptosis execution.

The Global Natural Products Social Molecular Networking (GNPS) resource and the DEREPLICATOR algorithm provide new tools for analyzing mass spectral data and enabling natural products discovery.

The role of RAS dimerization in tumor biology is an emerging area of preclinical cancer research. Characterization of a RAS monobody indicates that dimer formation is required for RAS signaling, revealing the dimer interface as a potential drug target.

Small-molecule control of transcriptional activation and genome editing was achieved by tethering inducible protein degron domains to an engineered CRISPR–Cas9 system.

A genetic screening approach using chemically mutagenized haploid mouse embryonic stem cells combined with next-generation sequencing identified recessive suppressor point mutations that elicit resistance to 6-thioguanine.

Mass spectrometry analysis of stromal extracts reveal a peptidolytic cascade in the plant chloroplast consisting of oligopeptidases and aminopeptidases that mediates the complete degradation of signal peptides to free amino acids.

A strategy called footprinting of long 7-deazaguanine-substituted RNA (FOLDeR) enables the identification of RNA G quadruplexes in long RNA.

Structural and biochemical studies of the histone acetyltransferase p300 in complex with acyl-CoA substrates reveal a lysine binding channel that accommodates a particular chain length to mediate efficient histone modification.

Aggregated mass spectral data by consortia such as the Global Natural Products Social (GNPS) molecular networking infrastructure enable natural product discovery. DEREPLICATOR, validated on peptidic natural products, is a computational tool to identify known metabolites in complex samples.

A systems-level look at the activation of joint synovial fibroblasts in rheumatoid arthritis patients in response to different activators and therapeutic kinase inhibitors shows that multivariate inhibitor effects depend on the nature of the activator, not on the disease state per se.

Inhibitors of the post-proline-cleaving serine proteases DPP8 and DPP9 trigger a lytic form of programmed cell death called pyroptosis by activating pro-caspase-1 without autoproteolysis.

Carbapenem β-lactam antibiotics target non-classical transpeptidases, the L,D-transpeptidases, which act in an alternative Mycobacterium tuberculosis peptidoglycan synthesis pathway, informing the design of evolved carbapenems with improved antibacterial activity.

A monobody was identified that binds to an allosteric lobe at the α4-β6-α5 interface to block H- and K-RAS signaling and transformation by disrupting RAS dimerization and nanoclustering.

Characterization of five enzymes involved in gibberellin production in rhizobia completes the elucidation of its biosynthetic pathway and indicates that bacteria have independently evolved this pathway separate from the ones found in plants and fungi.

Engineering of temperature-sensitive DNA repressors led to thermal bioswitches, allowing Escherichia coli to respond sharply to temperature at tunable set points and enabling application to host diagnostics and disease therapy.

Arachidonyl and adrenoyl PE phospholipids generated by ACSL4, an acyl-CoA synthase, are doubly or triply oxidized by lipoxygenases and other iron-containing sources of oxidation to promote ferroptotic cell death.

ACSL4 is critical for induction of ferroptosis, a programmed form of necrotic cell death, through the production of long polyunsaturated fatty acids that can be inhibited in an in vivo ferroptosis model with a small molecule ACSL4 inhibitor.

Single-molecule high-resolution optical trapping techniques elucidate the molecular mechanisms underlying the unwinding of RNA duplexes by the helicase Mtr4p, including how it restricts directional translocation to duplex regions.

Hydrogen–deuterium (H/D) exchange combined with NMR spectroscopy analysis of nucleosomal arrays identified an acidic patch on ubiquitin that mediates chromatin decompaction and further supports that ubiquitin–ubiquitin interactions are needed for chromatin solubilization.

A sulfonamide series lacking the prototypical side chain behave as full antagonists or inverse agonists of estrogen receptor (ERα) signaling in a graded fashion dependent on coactivator recruitment and helix-11 positioning.

Computational design enables the generation of a chimeric construct of the RAS exchange factor SOS that is specifically activated by a small molecule. The expression of this construct in different cell types reveals distinct phosphorylation kinetics.