The Pseudokinase TRIB1 in Immune Cells and Associated Disorders.

Research advances in Tribbles homolog (TRIB) genes have established the consensus that this protein family plays roles in diverse biological conditions and regulates intracellular signaling networks and several human diseases. In this review, we focus on one member of the family, TRIB1, and its role at the crossroads of immune signaling. TRIB1 directly interacts with transcription factors such as FOXP3 and C/EBPα, with several signaling molecules such as MEK1 and MALT1 and directly acts on key cell signaling pathways such as the MAPK and NF-κB pathways. Altogether, these interactions emphasize that TRIB1 is at the center of major cell signaling pathways while TRIB1 has cell-specific roles, potentially depending on the expressing cells and binding partners. In this review, we describe its roles in immune cells and highlight the interacting partners explaining these functions which suggests TRIB1 as a precise mediator of cellular homeostasis as well as in different cancers and immune-related disorders.

FaDA: A web application for regular laboratory data analyses.

Web-based data analysis and visualization tools are mostly designed for specific purposes, such as the analysis of data from whole transcriptome RNA sequencing or single-cell RNA sequencing. However, generic tools designed for the analysis of common laboratory data for noncomputational scientists are also needed. The importance of such web-based tools is emphasized by the continuing increases in the sample capacity of conventional laboratory tools such as quantitative PCR, flow cytometry or ELISA instruments. We present a web-based application FaDA, developed with the R Shiny package that provides users with the ability to perform statistical group comparisons, including parametric and nonparametric tests, with multiple testing corrections suitable for most standard wet-laboratory analyses. FaDA provides data visualizations such as heatmaps, principal component analysis (PCA) plots, correlograms and receiver operating curves (ROCs). Calculations are performed through the R language. The FaDA application provides a free and intuitive interface that allows biologists without bioinformatic skill to easily and quickly perform common laboratory data analyses. The application is freely accessible at https://shiny-bird.univ-nantes.fr/app/Fada.

Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity.

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, age-related impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality.

Tissue-specific transcriptome profiling of Drosophila reveals roles for GATA transcription factors in longevity by dietary restriction.

Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs. We predict and validate roles for the evolutionarily conserved GATA family of TFs, and identify conservation of this signal in mice. Importantly, restricting knockdown of the GATA TF srp to specific fly tissues recapitulated the benefits but not the costs of DR. Together, our data indicate that the GATA TFs mediate effects of dietary amino acids on lifespan, and that by manipulating them in specific tissues it is possible to reap the fitness benefits of EAAs, decoupled from a cost to longevity.