Stress granules and processing bodies are dynamically linked sites of mRNP remodeling

Abstract

Stress granules (SGs) are cytoplasmic aggregates of stalled translational preinitiation complexes that accumulate during stress. GW bodies/processing bodies (PBs) are distinct cytoplasmic sites of mRNA degradation. In this study, we show that SGs and PBs are spatially, compositionally, and functionally linked. SGs and PBs are induced by stress, but SG assembly requires eIF2α phosphorylation, whereas PB assembly does not. They are also dispersed by inhibitors of translational elongation and share several protein components, including Fas-activated serine/threonine phosphoprotein, XRN1, eIF4E, and tristetraprolin (TTP). In contrast, eIF3, G3BP, eIF4G, and PABP-1 are restricted to SGs, whereas DCP1a and 2 are confined to PBs. SGs and PBs also can harbor the same species of mRNA and physically associate with one another in vivo, an interaction that is promoted by the related mRNA decay factors TTP and BRF1. We propose that mRNA released from disassembled polysomes is sorted and remodeled at SGs, from which selected transcripts are delivered to PBs for degradation.

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

“…In yeast, stress treatment results in increased number of P bodies (Teixeira and Parker, 2007). However, in mammalian cells, bulk mRNAs are stored in stress granules upon stress treatment (Kedersha et al, 2005). Therefore, regulation of formation of P bodies in C. elegans resembles that in yeast and the formation of SGs in mammalian cells.…”

“…SGs are physically distinct and spatially separable from P bodies, playing a role in storage of translationally repressed mRNAs under stress conditions (Kimball et al, 2003;Kedersha et al, 2005). The assembly of SGs appears to be regulated by distinct signaling pathways in mammalian cells.…”

Principles and effects of microRNA-mediated post-transcriptional gene regulation

“…For instance, miR-16 may recruit TTP to canonical AREs through the members of the Argonaute family. Interestingly, TTP forms a complex with hDcp1a, hDcp2 and hXrn1, and overexpressed TTP colocalizes with PBs (Jing et al, 2005;Kedersha et al, 2005;Lykke-Andersen and Wagner, 2005). Moreover, the ARE binding protein HuR involved in reversing the miR-122-mediated repression of the CAT-1 mRNA (Bhattacharyya et al, 2006).…”

Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins (G3BP)

“…Further evidence that G3BP1 can control the abundance of certain mRNAs was obtained when it was found in stress granules (Tourriere et al, 2003). Stress granules are sites of abortive translation initiation complexes that contain translational factors, small ribosomal subunits as well as untranslated mRNAs (Tourriere et al, 2003;Kedersha et al, 2005). It is not presently known whether G3BP2 can bind mRNA or regulate its stability.…”