Genetic efficiency in higher organisms depends on mechanisms to create multiple functions from single genes. To investigate this question for an enzyme family, we chose aminoacyl tRNA synthetases (AARSs). They are exceptional in their progressive and accretive proliferation of noncatalytic domains as the Tree of Life is ascended. Here we report discovery of a large number of natural catalytic nulls (CNs) for each human AARS. Splicing events retain noncatalytic domains while ablating the catalytic domain (CD) to create CNs with diverse functions. Each synthetase is converted into several new signaling proteins with biological activities ‘orthogonal’ to that of the catalytic parent. We suggest that splice variants with non-enzymatic functions may be more general, as evidenced by recent findings of other catalytically inactive splice-variant enzymes.

Viral infection is controlled by host innate immune cells that express specialized receptors for viral components. Engagement of these pattern recognition receptors triggers a series of signaling pathways that culminate in the production of antiviral mediators such as type I interferons. Mitochondrial antiviral-signaling protein (MAVS) acts as a central hub for signal transduction initiated by RIG-I-like receptors, which predominantly recognize viral RNA. MAVS expression and function are regulated by both post-transcriptional and post-translational mechanisms, of which ubiquitination and phosphorylation play the most important roles in modulating MAVS function. Increasing evidence indicates that viruses can escape the host antiviral response by interfering at multiple points in the MAVS signaling pathways, thereby maintaining viral survival and replication. This review summarizes recent studies on the mechanisms by which MAVS expression and signaling are normally regulated and on the various strategies employed by viruses to antagonize MAVS activity, which may provide new insights into the design of novel antiviral agents.

Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction of apoptosis, and inhibition of energy metabolism. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is a member of the evolutionarily highly conserved Sir2 (silent information regulator 2) superprotein family, which is located in the nucleus and cytoplasm. It can deacetylate protein substrates in various signal transduction pathways to regulate gene expression, cell apoptosis and senescence, participate in the process of neuroprotection, energy metabolism, inflammation and the oxidative stress response in living organisms, and plays an important role in toxic damage caused by toxicants and in the process of SIRT1 activator/inhibitor antagonized toxic damage. This review summarizes the role that SIRT1 plays in toxic damage caused by toxicants via its interactions with protein substrates in certain signaling pathways.

The poor durability of Pt-based nanoparticles dispersed on carbon black is the challenge for the application of long-life polymer electrolyte fuel cells. Recent work suggests that Fe- and N-codoped carbon (Fe–N–C) might be a better support than conventional high-surface-area carbon. In this work, we find that the electrochemical surface area retention of Pt/Fe–N–C is much better than that of commercial Pt/C during potential cycling in both acidic and basic media. In situ inductively coupled plasma mass spectrometry studies indicate that the Pt dissolution rate of Pt/Fe–N–C is 3 times smaller than that of Pt/C during cycling. Density functional theory calculations further illustrate that the Fe–N–C substrate can provide strong and stable support to the Pt nanoparticles and alleviate the oxide formation by adjusting the electronic structure. The strong metal–substrate interaction, together with a lower metal dissolution rate and highly stable support, may be the reason for the significantly enhanced stability of Pt/Fe–N–C. This finding highlights the importance of carbon support selection to achieve a more durable Pt-based electrocatalyst for fuel cells.