Multiple Processing Body Factors and the ARE Binding Protein TTP Activate mRNA Decapping

Abstract

Decapping is a key step in mRNA turnover. However, the composition and regulation of the human decapping complex is poorly understood. Here, we identify three proteins that exist in complex with the decapping enzyme subunits hDcp2 and hDcp1: hEdc3, Rck/p54, and a protein in decapping we name Hedls. Hedls is important in decapping because it enhances the activity of the catalytic hDcp2 subunit and promotes complex formation between hDcp2 and hDcp1. Specific decapping factors interact with the mRNA decay activators hUpf1 and TTP, and TTP enhances decapping of a target AU-rich element (ARE) RNA in vitro. Each decapping protein localizes in cytoplasmic processing bodies (PBs), and overexpression of Hedls produces aberrant PBs and concomitant accumulation of a deadenylated ARE-mediated mRNA decay intermediate. These observations suggest that multiple proteins involved in human decapping are important subunits of PBs and are activated on ARE-mRNAs by the protein TTP.

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

“…GWB are named from the marker protein GW182, which contains multiple glycine (G) and tryptophan (W) repeats and a classic RNA binding domain at the carboxyl terminus (Eystathioy et al, 2002a). The mRNA decay factors/complexes found in GWB include the deadenylase Ccr4, the decapping complex Dcp1a/1b/Dcp2, the LSm1-7 complex, Ge-1 (also known as Hedls), rck/p54, and exonuclease Xrn1 (Bashkirov et al, 1997;van Dijk et al, 2002;Ingelfinger et al, 2002;Lykke-Andersen, 2002;Eystathioy et al, 2003;Cougot et al, 2004;Andrei et al, 2005;Yu et al, 2005;Fenger-Gron et al, 2005). GWB are physically juxtaposed to and transiently interact with stress granules (SG).…”

The self-interaction of native TDP-43 C terminus inhibits its degradation and contributes to early proteinopathies

“…Additionally, a self-perpetuating Q/N-rich domain of apCPEB was suggested to participate in the long-term facilitation of Aplysia 31 . A set of proteins that control the stability of mRNAs as well as their translational silencing are colocalised in the cytoplasmic foci called processing bodies or P-bodies 38 . Interestingly, several P-body components contain a potential prionogenic domain.…”

Ataxin-2 Interacts with the DEAD/H-Box RNA Helicase DDX6 and Interferes with P-Bodies and Stress Granules

“…The human protein CCR4, which is involved in mRNA deadenylation, the decapping stimulating LSm proteins LSm1-7, the DEAD/Hbox RNA helicase DDX6 (also known as RCK/p54), GW182, and Ge-1 are components of P-bodies (Bouveret et al, 2000;Eystathioy et al, 2002;Ingelfinger et al, 2002; LykkeAndersen, 2002;Cougot et al, 2004;Yu et al, 2005). Moreover, the RNA-associated protein 55, hEDC3, Hedls as well as factors of the RISC complex localize to P-bodies in mammalian cells (Fenger-Gron et al, 2005;Liu et al, 2005;Sen and Blau, 2005;Yang et al, 2006). P-bodies represent dynamic structures that are in an equilibrium with polysomes and contain nontranslating mRNA .…”