Hydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematode Caenorhabditis elegans that processes information perceived by two sensory neurons to control the induction of hydrogen peroxide defenses in the organism. We found that catalases produced by Escherichia coli, the nematode’s food source, can deplete hydrogen peroxide from the local environment and thereby protect the nematodes. In the presence of E. coli, the nematode’s neurons signal via TGFβ-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen peroxide defenses. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.

Oxidative stress alters cell viability, from microorganism irradiation sensitivity to human aging and neurodegeneration. Deleterious effects of protein carbonylation by reactive oxygen species (ROS) make understanding molecular properties determining ROS susceptibility essential. The radiation-resistant bacterium Deinococcus radiodurans accumulates less carbonylation than sensitive organisms, making it a key model for deciphering properties governing oxidative stress resistance. We integrated shotgun redox proteomics, structural systems biology, and machine learning to resolve properties determining protein damage by c-irradiation in Escherichia coli and D. radiodurans at multiple scales. Local accessibility, charge, and lysine enrichment accurately predict ROS susceptibility. Lysine, methionine, and cysteine usage also contribute to ROS resistance of the D. radiodurans proteome. Our model predicts proteome maintenance machinery, and proteins protecting against ROS are more resistant in D. radiodurans. Our findings substantiate that protein-intrinsic protection impacts oxidative stress resistance, identifying causal molecular properties.

Bacterial mRNAs have short life cycles, in which transcription is rapidly followed by translation and degradation within seconds to minutes. The resulting diversity of mRNA molecules across different life-cycle stages impacts their functionality but has remained unresolved. Here we quantitatively map the 3’ status of cellular RNAs in Escherichia coli during steady-state growth and report a large fraction of molecules (median>60%) that are fragments of canonical full-length mRNAs. The majority of RNA fragments are decay intermediates, whereas nascent RNAs contribute to a smaller fraction. Despite the prevalence of decay intermediates in total cellular RNA, these intermediates are underrepresented in the pool of ribosome-associated transcripts and can thus distort quantifications and differential expression analyses for the abundance of full-length, functional mRNAs. The large heterogeneity within mRNA molecules in vivo highlights the importance in discerning functional transcripts and provides a lens for studying the dynamic life cycle of mRNAs.

Bacterial mRNAs have short life cycles, in which transcription is rapidly followed by translation and degradation within seconds to minutes. The resulting diversity of mRNAs impacts their functionality but has remained unresolved. Here we quantitatively map the 3’ status of cellular RNAs in Escherichia coli during steady-state growth and report a large fraction of molecules (median>60%) that are fragments of canonical full-length mRNAs. The majority of RNA fragments are decay intermediates following endonuclease cleavage by RNase E and yet-unknown nucleases, whereas nascent RNAs contribute to a smaller fraction. Despite the prevalence of decay intermediates in total RNA, they are underrepresented in the pool of ribosome-associated transcripts and can thus distort quantifications for the abundance of full-length, functional mRNAs. The large heterogeneity within mRNA molecules in vivo highlights the importance in discerning functional transcripts and provides a lens for studying the dynamic life cycle of mRNAs.

Oxidative stress alters cell viability, from microorganism irradiation sensitivity to human aging and neurodegeneration. Deleterious effects of protein carbonylation by reactive oxygen species 20

AbstractHydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematode Caenorhabditis elegans that processes information perceived by two sensory neurons to control the induction of hydrogen-peroxide defenses in the organism. We found that catalases produced by Escherichia coli, the nematode’s food source, can deplete hydrogen peroxide from the local environment and thereby protect the nematodes. In the presence of E. coli, the nematode’s neurons signal via TGFβ-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen-peroxide defenses. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.

No abstract

Two-state ratiometric biosensors change conformation and spectral properties in response to specific biochemical inputs. Much effort over the past two decades has been devoted to engineering biosensors specific for ions, nucleotides, amino acids, and biochemical potentials.The utility of these biosensors is diminished by empirical errors in fluorescence-ratio signal measurement, which reduce the range of input values biosensors can measure accurately.Here, we present a formal framework and a web-based tool, the SensorOverlord, that predicts the input range of two-state ratiometric biosensors given the experimental error in measuring their signal. We demonstrate the utility of this tool by predicting the range of values that can be measured accurately by biosensors that detect pH, NAD + , NADH, NADPH, histidine, and glutathione redox potential. The SensorOverlord enables users to compare the predicted accuracy of biochemical measurements made with different biosensors, and subsequently select biosensors that are best suited for their experimental needs.