2016-11-14Ferroptosis 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.
2016-11-07New 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.
2016-11-28The iron (Fe) proteins of molybdenum (Mo) and vanadium (V) nitrogenases mimic carbon monoxide (CO) dehydrogenase in catalyzing the interconversion between CO2 and CO under ambient conditions. Catalytic reduction of CO2 to CO is achieved in vitro and in vivo upon redox changes of the Fe-protein-associated [Fe4S4] clusters. These observations establish the Fe protein as a model for investigation of CO2 activation while suggesting its biotechnological adaptability for recycling the greenhouse gas into useful products.
2016-11-07RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-substituted RNAs (FOLDeR), that allows the formation of G4s to be confirmed in long RNAs and under functional conditions.
2016-10-31In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.
2016-10-31Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions—including dose, time, specificity, and mutually exclusive modulation of multiple genes—are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation.
2016-10-31Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within chloroplasts of Arabidopsis thaliana are degraded to amino acids by a multi-step peptidolytic cascade consisting of oligopeptidases and aminopeptidases, effectively allowing the recovery of single amino acids within these organelles.