Translational control mediated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2␣) is central to stress-induced programs of gene expression. Trypanosomatids, important human pathogens, display differentiation processes elicited by contact with the distinct physiological milieu found in their insect vectors and mammalian hosts, likely representing stress situations. Trypanosoma brucei, the agent of African trypanosomiasis, encodes three potential eIF2␣ kinases (TbeIF2K1 to -K3). We show here that TbeIF2K2 is a transmembrane glycoprotein expressed both in procyclic and in bloodstream forms. The catalytic domain of TbeIF2K2 phosphorylates yeast and mammalian eIF2␣ at Ser51. It also phosphorylates the highly unusual form of eIF2␣ found in trypanosomatids specifically at residue Thr169 that corresponds to Ser51 in other eukaryotes. T. brucei eIF2␣, however, is not a substrate for GCN2 or PKR in vitro. The putative regulatory domain of TbeIF2K2 does not share any sequence similarity with known eIF2␣ kinases. In both procyclic and bloodstream forms TbeIF2K2 is mainly localized in the membrane of the flagellar pocket, an organelle that is the exclusive site of exo-and endocytosis in these parasites. It can also be detected in endocytic compartments but not in lysosomes, suggesting that it is recycled between endosomes and the flagellar pocket. TbeIF2K2 location suggests a relevance in sensing protein or nutrient transport in T. brucei, an organism that relies heavily on posttranscriptional regulatory mechanisms to control gene expression in different environmental conditions. This is the first membrane-associated eIF2␣ kinase described in unicellular eukaryotes.

The world is experiencing the worst global health crisis in recent decades since December/2019 due to a new pandemic coronavirus. The COVID-19 disease, caused by SARS-CoV-2, has resulted in more than 30 million cases and 950 thousand deaths worldwide as of September 21, 2020. Determining the extent of the virus on public surfaces is critical for understanding the potential risk of infection in these areas. In this study, we investigated the presence of SARS-CoV-2 RNA on public surfaces in a densely populated urban area in Brazil. Forty-nine of 933 samples tested positive (5.25%) for SARS-CoV-2 RNA, including samples collected from distinct material surfaces, including metal and concrete, and distinct places, mainly around hospital care units and public squares. Our data indicated the contamination of public surfaces by SARS-CoV-2, suggesting the circulation of infected patients and the risk of infection for the population. Constant monitoring of the virus in urban areas is required as a strategy to fight the pandemic and prevent further infections.

Graphical AbstractHighlights d eEF2 kinase enhances the accuracy of protein synthesis under a range of conditions d mTORC1 inhibition improves translation accuracy by activating eEF2K d eEF2K assists correct start codon selection during translation initiation d Impairing translation fidelity reduces lifespan in C. elegans In BriefXie et al. report that eukaryotic elongation factor 2 kinase (eEF2K), which impairs the rate of elongation, decreases misreading or termination readthrough errors and promotes the correct recognition of start codons in mRNAs. Depletion of the eEF2K ortholog or other factors implicated in translation fidelity in C. elegans decreases lifespan.

Background: IMPACT inhibits GCN2, a kinase that directs stress remedial responses by attenuating translation and controls feeding behavior and memory. Results: Neuronal IMPACT is developmentally up-regulated, promoting protein synthesis and neuritogenesis, opposing GCN2. Conclusion: GCN2 and IMPACT modulate an early step in neuronal differentiation. Significance: A neuron-specific developmental program is controlled by two evolutionarily conserved translational regulators.

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