Embryonic stem cell (ESC) differentiation and somatic cell reprogramming are biological processes governed by antagonistic expression or repression of a largely common set of genes. Accurate regulation of gene expression is thus essential for both processes, and alterations in RNA processing are predicted to negatively affect both. We show that truncation of the DIDO gene alters RNA splicing and transcription termination in ESC and mouse embryo fibroblasts (MEF), which affects genes involved in both differentiation and reprogramming. We combined transcriptomic, protein interaction, and cellular studies to identify the underlying molecular mechanism. We found that DIDO3 interacts with the helicase DHX9, which is involved in R-loop processing and transcription termination, and that DIDO3-exon16 deletion increases nuclear R-loop content and causes DNA replication stress. Overall, these defects result in failure of ESC to differentiate and of MEF to be reprogrammed. MEF immortalization restored impaired reprogramming capacity. We conclude that DIDO3 has essential functions in ESC differentiation and somatic cell reprogramming by supporting accurate RNA metabolism, with its exon16-encoded domain playing the main role.

The primary contact between the fungal phytopathogen Botrytis cinerea and its host takes place at the cell surface of both organisms. The fungal cell wall is generally composed of an inner skeletal layer consisting of various polysaccharides surrounded by a layer of glycoproteins. Some of these glycoproteins have structural or enzymatic functions, or are involved in conidial adhesion. After landing on the host surface and sensing appropriate signals, B. cinerea conidia produce a germ tube and secrete phytotoxic fungal metabolites and cell wall-degrading enzymes (CWDEs), facilitating host penetration. In fact, 118 genes encoding putative Carbohydrate-Active Enzymes (CAZymes) have been identified in the B. cinerea genome. This large enzymatic repertoire could explain, at least in part, the ability of B. cinerea to infect a vast number of plant species. In recent years, several genes and signaling factors have been identified as playing key roles in pathogenesis, particularly in appressorium formation and penetration. These include the NOX Complex, MAPK cascades, heterotrimeric G proteins, histidine kinases and cAMP signaling pathways. Some of these pathways could also be responsible for controlling the expression and secretion of CWDEs and/or secondary metabolites during infection. Herein, putative virulence factors that are linked to the cell wall, as well as recentlydescribed genes and components that allow the sensing of environmental cues, are highlighted.

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