title: The role of disordered protein regions in the assembly of decapping complexes and RNP granules.
abstract: The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping factors orchestrate the recruitment and activity of this complex in vivo. These factors include enhancer of decapping 3 (EDC3), EDC4, like Sm14A (LSm14A), Pat, the LSm1-7 complex, and the RNA helicase DDX6. Decapping factors are often modular and feature folded domains flanked or connected by low-complexity disordered regions. Recent studies have made important advances in understanding how these disordered regions contribute to the assembly of decapping complexes and promote phase transitions that drive RNP granule formation. These studies have also revealed that the decapping network is governed by interactions mediated by short linear motifs (SLiMs) in these disordered regions. Consequently, the network has rapidly evolved, and although decapping factors are conserved, individual interactions between orthologs have been rewired during evolution. The plasticity of the network facilitates the acquisition of additional subunits or domains in pre-existing subunits, enhances opportunities for regulating mRNA degradation, and eventually leads to the emergence of novel functions.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jonas
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D012261:Ribonucleoproteins; C030052:mRNA decapping enzymes; D004722:Endoribonucleases
keywords: DCP2; SLiMs; decapping; mRNA decay