[Frontier leaders] Of nature and nurture: connecting gene regulation, metabolism and disease

Frontier Leaders Seminar

Title: Of nature and nurture: connecting gene regulation, metabolism and disease

Speaker: Matthias Hentze

Affiliation: Director of the EMBL
                  Professor of of Molecular Medicine at the University of Heidelberg, Germany

Abstract:

RNA-binding proteins (RBPs) orchestrate virtually all aspects of RNA biology. I will describe the development of “mRNA Interactome capture” as a technique that allows to chart “all” active RBPs in living cells and that led to the identification of hundreds of new RBPs from HeLa cells (1,2). The described method is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings and cell types. Interactome data from murine embryonic stem cells (3), hepatocytic Huh-7 cells and yeast (unpublished) shed new light on diverse aspects of RNA biology, including RBPs in disease and novel RNA-binding architectures (4). We identify dozens of 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 (5).

(1) Castello et al., Cell 149, 1393-1406, 2012
(2) Castello et al., Nature Protoc. 8, 491-500, 2013
(3) Kwon et al., Nature Struc. Mol. Biol. 20, in press, 2013
(4) Castello et al., Trends i Genet. 29, 318-327, 2013
(5) Hentze and Preiss, TiBS 35, 423-426, 2010