Matthias W. Hentze, European Molecular Biology Laboratory, Heidelberg, Germany
RNA-binding proteins (RBPs) orchestrate virtually all aspects of RNA biology. I plan to speak about rapidly progressing new work identifying “all” mRNA binding proteins (the “mRNA interactomes”) of mammalian cells and yeast using a new system-wide approach that we refer to as “Interactome capture”. Employing two complementary protocols for covalent UV-crosslinking of RBPs to RNA, we have identified 860 RBPs fom HeLa cells that are significantly enriched over negative controls shown by analysis of independent repeat experiments. Following validation, the in vivo HeLa mRNA interactome adds more than three hundred RBPs to those previously known. The described method is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings. These data shed new light on diverse aspects of RNA biology, including RBPs in disease and novel RNA-binding architectures. We also identify enzymes of intermediary metabolism that moonlight as RBPs in vivo, implicating these in the recently proposed REM (RNA/enzyme/metabolite) networks for the coordination of cell metabolism and gene expression.