title: RNA-binding proteins in Mendelian disease.
abstract: RNA-binding proteins (RBPs) control all aspects of RNA fate, and defects in their function underlie a broad spectrum of human pathologies. We focus here on two recent studies that uncovered the in vivo mRNA interactomes of human cells, jointly implicating over 1100 proteins in RNA binding. Surprisingly, over 350 of these RBPs had no prior RNA binding-related annotation or domain homology. The datasets also contain many proteins that, when mutated, cause Mendelian diseases, prominently neurological, sensory, and muscular disorders and cancers. Disease mutations in these proteins occur throughout their domain architectures and many are found in non-classical RNA-binding domains and in disordered regions. In some cases, mutations might cause disease through perturbing previously unknown RNA-related protein functions. These studies have thus expanded our knowledge of RBPs and their role in genetic diseases. We also expect that mRNA interactome capture approaches will aid further exploration of RNA systems biology in varied physiological and pathophysiological settings.
authors: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors: Alfredo
authors: A
authors: Castello
authors: Bernd
authors: B
authors: Fischer
authors: Matthias W
authors: MW
authors: Hentze
authors: Thomas
authors: T
authors: Preiss
mesh_terms: D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins