Uncharged tRNA Activates GCN2 by Displacing the Protein Kinase Moiety from a Bipartite tRNA-Binding Domain

Protein kinase GCN2 regulates translation in amino acid–starved cells by phosphorylating eIF2. GCN2 contains a regulatory domain related to histidyl-tRNA synthetase (HisRS) postulated to bind multiple deacylated tRNAs as a general sensor of starvation. In accordance with this model, GCN2 bound several deacylated tRNAs with similar affinities, and aminoacylation of tRNAPhe weakened its interaction with GCN2. Unexpectedly, the C-terminal ribosome binding segment of GCN2 (C-term) was required in addition to the HisRS domain for strong tRNA binding. A combined HisRS+C-term segment bound to the isolated protein kinase (PK) domain in vitro, and tRNA impeded this interaction. An activating mutation (GCN2c-E803V) that weakens PK–C-term association greatly enhanced tRNA binding by GCN2. These results provide strong evidence that tRNA stimulates the GCN2 kinase moiety by preventing an inhibitory interaction with the bipartite tRNA binding domain

THE DESIGN OF A LEARNING ANALYTICS DASHBOARD: EDUOPEN MOOC PLATFORM REDEFINITION PROCEDURES

The current EduOpen dashboard is not capable of monitoring performances and trends over the medium to long term both for the students as for the instructors; summarising and synthesising the adequate information; allowing implementation of any sort of predictive actions and functions (learning prediction). The article aims to expose the process of innovation and redefinition of a learning analytics dashboard in the EduOpen MOOC platform in order to define a model to design it accurately in terms of productivity for all users (teachers and students above all). From the literature analysis, main MOOC platform comparisons and the insights from the round tables a time spent variable is identified as at the basis of the entire user experience in online training paths. A concrete experimentation, through the design of a learning timeline and a constructive feedback system of an upcoming course in the EduOpen catalogue, is designed and explained relaying on the hypothesis of the existence of a correlation between the “time spent” (time value) and the final performance of the student