The highly conserved eukaryotic DRG factors are required for efficient translation in a manner redundant with the putative RNA helicase Slh1

Eukaryotic and archaeal DRG factors are highly conserved proteins with characteristic GTPase motifs. This suggests their implication in a central biological process, which has so far escaped detection. We show here that the two Saccharomyces cerevisiae DRGs form distinct complexes, RBG1 and RBG2, and that the former co-fractionate with translating ribosomes. A genetic screen for triple synthetic interaction demonstrates that yeast DRGs have redundant function with Slh1, a putative RNA helicase also associating with translating ribosomes. Translation and cell growth are severely impaired in a triple mutant lacking both yeast DRGs and Slh1, but not in double mutants. This new genetic assay allowed us to characterize the roles of conserved motifs present in these proteins for efficient translation and/or association with ribosomes. Altogether, our results demonstrate for the first time a direct role of the highly conserved DRG factors in translation and indicate that this function is redundantly shared by three factors. Furthermore, our data suggest that important cellular processes are highly buffered against external perturbation and, consequently, that redundantly acting factors may escape detection in current high-throughput binary genetic interaction screens

Regulation of Cellular Metabolism through Phase Separation of Enzymes

Metabolism is the sum of the life-giving chemical processes that occur within a cell. Proper regulation of these processes is essential for all organisms to thrive and prosper. When external factors are too extreme, or if internal regulation is corrupted through genetic or epigenetic changes, metabolic homeostasis is no longer achievable and diseases such as metabolic syndrome or cancer, aging, and, ultimately, death ensue. Metabolic reactions are catalyzed by proteins, and the in vitro kinetic properties of these enzymes have been studied by biochemists for many decades. These efforts led to the appreciation that enzyme activities can be acutely regulated and that this regulation is critical to metabolic homeostasis. Regulation can be mediated through allosteric interactions with metabolites themselves or via post-translational modifications triggered by intracellular signal transduction pathways. More recently, enzyme regulation has attracted the attention of cell biologists who noticed that change in growth conditions often triggers the condensation of diffusely localized enzymes into one or more discrete foci, easily visible by light microscopy. This reorganization from a soluble to a condensed state is best described as a phase separation. As summarized in this review, stimulus-induced phase separation has now been observed for dozens of enzymes suggesting that this could represent a widespread mode of activity regulation, rather than, or in addition to, a storage form of temporarily superfluous enzymes. Building on our recent structure determination of TOROIDs (TORc1 Organized in Inhibited Domain), the condensate formed by the protein kinase Target Of Rapamycin Complex 1 (TORC1), we will highlight that the molecular organization of enzyme condensates can vary dramatically and that future work aimed at the structural characterization of enzyme condensates will be critical to understand how phase separation regulates enzyme activity and consequently metabolic homeostasis. This information may ultimately facilitate the design of strategies to target the assembly or disassembly of specific enzymes condensates as a therapeutic approach to restore metabolic homeostasis in certain diseases

Contrôles épigénétiques, développement et variation génétique naturelle chez les plantes

Les plantes se distinguent de la plupart des animaux par leur absence de mobilité. Cette vie statique les contraint à faire face aux agressions et aux autres changements de l’environnement à l’aide de réponses physiologiques et de modes de développement appropriés. Chez les végétaux, l’embryogenèse cesse peu après la mise en place de deux groupes de cellules souches, les méristèmes racinaire et caulinaire, qui produiront après germination, de manière itérative, tiges, feuilles et racines. Cette organogenèse post-embryonnaire est particulièrement sensible aux conditions du milieu, ce qui confère aux plantes une plasticité phénotypique rarement observée dans le monde animal. Par ailleurs, alors que chez l’animal la lignée germinale est établie tôt au cours du développement, les fleurs sont élaborées tardivement et à partir de méristèmes ayant préalablement participé au développement végétatif des parties aériennes. Enfin, les plantes se singularisent par des capacités de dédifférenciation et de régénération presque illimitées, qui s’expliquent par le fait que, chez ces espèces, l’identité des cellules est déterminée moins par le lignage que par le positionnement. Il est donc raisonnable de penser que les mécanismes de mémoire cellulaire, et notamment ceux reposant sur la chromatine, jouent un rôle moindre dans le développement des végétaux que dans celui de la plupart des animaux. Cependant, la méthylation de l’ADN, ainsi que de nombreuses autres modifications chromatiniennes associées à l’activation ou l’inactivation stable de la transcription au travers des divisions cellulaires sont trouvées dans ces deux règnes. De fait, nous décrirons dans cet article plusieurs processus épigénétiques bien étayés chez les plantes. Néanmoins, il semble que ceux-ci contribuent plus à la production de variants d’expression transmis au travers des générations qu’à la régulation de l’expression génique au cours du développement.Plant life strategies differ radically from those of most animals. Plants are not motile, and can only face stress by developing appropriate physiological responses. In addition, many developmental decisions take place during post-embryonic life in plants, whereas vertebrate and invertebrate development is nearly complete by the time of birth. For instance, while the germ line is typically set aside early during embryogenesis in animals, plants produce gametes from stem cell populations that were previously used for the vegetative growth of shoots. Nevertheless, plants and animals have similar nuclear organization, chromatin constitution and gene content, which raises the question as to whether or not fundamental differences in the use of genetic information underlie their distinct life strategies. More specifically, we would like to know if chromatin and the epigenetically defined, heritable cell fates that it can confer play comparable roles in plants and animals. Here we review our current knowledge on chromatin-mediated epigenetic processes in plants. Based on available evidence, we argue that epigenetic regulation of gene expression plays a relatively minor role in plants compared to mammals. Conversely, plants appear to be more prone than other multicellular organisms to the induction of chromatin-based, epigenetically modified gene activity states that can be transmitted over many generations. These so-called “epimutations” may therefore represent a significant proportion of the natural genetic variation seen in plants. In humans, epimutations are frequently observed in cancers, and given their metastable nature, they could also play an important role in familial disorders that do not demonstrate clear Mendelian inheritance

Contribution à l'étude des protéines de la famille des tristétraprolines (rôle de la protéine CTH2 de saccharomyces cerevisae dans le contrôle de la maturation et de la dégradation de certains ARN messagers)

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Manuscript_DBPR-NSMB-A45852 RAW DATA

AbstractRaw data of all Figures and Extended Figures of the manuscript DBPR-NSMB-A45852