It is known that over expression of one single transcription factor, C/EBPa, is sufficient to convert B cells into macrophages thus regulating the transdifferentiation towards different lineages. However, the molecular mechanisms through which cells acquire a new fate are still unclear. Chris Van Oevelen, from the Thomas Graf’s lab at CRG, showed that C/EBPa binds a class of specific enhancers into macrophages that are inactive and that, upon binding, are activated and induce a delayed up-regulation of nearby macrophage genes.
AU-rich elements (AREs) are known to regulate the mRNA stability and about the 16% of human mRNAs contain this element. The sequence is recognized by specific ARE binding proteins (AUBPs) as AUF1 that, when downregulated in mice, induce different developmental alterations as the reduction of skeletal muscle mass and muscle weakness. Schneider’lab results suggest that this phenotype is due to the prolonged and massive activation of satellite stem cells that could not differentiate into skeletal muscle cells.
RNA binding proteins are multifunctional factors that have a key role in the regulation of gene expression. Among them, Upstream of N-Ras (UNR) seems to be involved in mRNA regulation at the levels of translation and stability. In a tumor context, depletion of UNR modifies cancer specifics properties as growth and clonogenicity of melanoma cells. On the other hand, its over expression in primary cell cultures induces transformation. Even if many RNA targets were identified, its function is still under investigation in Fatima Gebauer’s lab.
CRG Symposium 2014