Processing bodies (PBs) and Stress granules (SGs) are the founding members of a new class of RNA granules, known as mRNA silencing foci, as they harbor transcripts circumstantially excluded from the translationally active pool. PBs and SGs are able to release mRNAs thus allowing their translation. PBs are constitutive, but respond to stimuli that affect mRNA translation and decay, whereas SGs are specifically induced upon cellular stress, which triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor elF2alpha, and tRNA cleavage among others. PBs and SGs with different composition may coexist in a single cell. These macromolecular aggregates are highly conserved through evolution, from unicellular organisms to vertebrate neurons. Their dynamics is regulated by several signaling pathways, and depends on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins frequently present in neurodegenerative diseases, and may play a role in the pathology. Virus infections may induce or impair SG formation. Besides being important for mRNA regulation upon stress, SGs modulate the signaling balancing apoptosis and cell survival. Finally, the formation of nuclear stress bodies (nSBs), which share components with SGs, and the assembly of additional cytosolic aggregates containing RNA-the UV granules and the Ire1 foci-, all them induced by specific cell damage factors, contribute to cell survival.
SummaryMammalian Staufen 1 is recruited to stress granules and impairs their assembly Journal of Cell Science 564 is considered to be a global mRNA-binding factor, as it was shown to bind to different RNA motifs, including G-quartets, the β-actin zip code, the Myc 3ЈUTR; the FMR1 3ЈUTR, the HIV transactivating response region and the so-called Staufen-binding motif (Rackham and Brown, 2004;Dugré-Brisson et al., 2005; Kim, Y. K. et al., 2005). Recently, at least 7% of cellular mRNAs were shown to be present in Stau1 ribonucleoparticles (RNPs) (Furic et al., 2008). Consistently with this broad spectrum of targets, Staufen was associated with a variety of cytosolic functions. Staufen is involved in mRNA transport in both oocytes and somatic cells in vertebrates, as well as in invertebrates (Ferrandon et al., 1994;Broadus et al., 1998; Kiebler et al., 1999;Micklem et al., 2000;Tang et al., 2001;Belanger et al., 2003;Yoon and Mowry, 2004;Gautrey et al., 2005; Lebeau et al., 2008;Vessey et al., 2008). When bound to the 3ЈUTR, mammalian Stau1 triggers mRNA decay by recruitment of UPF1, a key molecule for mRNA degradation (Kim, Y. K. et al., 2005). By contrast, it enhances CAP-dependent translation when tethered to the 5ЈUTR (Dugré-Brisson et al., 2005). In addition to these cytoplasmic functions, nuclear roles for mammalian Stau1 molecules have begun to emerge (Kiebler et al., 2005). Whether Stau1 functions contribute to stress granule physiology is unknown.In this work we show that, although mammalian Stau1 is always present in stress granules, either induced by cellular stress or by pharmacological inhibition of translation initiation, is not an essential component of these foci. Moreover, we found that Stau1 depletion facilitated stress granule assembly, whereas transfection of Stau1 constructs inhibited their formation. Processing body integrity was moderately affected by Stau1, according to our finding that Stau1 is scarcely recruited to these structures. We show that Stau1 associates with polysomes, protecting them from stressinduced breakdown. We propose that downstream of the stress signaling, the breakdown of polysomes and concomitant stress granule formation are regulated by Stau1. Results Presence of Stau1 in stress granules and processing bodiesWe have previously shown that Stau1 is recruited to stress granules in brain primary cell cultures upon induction of oxidative stress . Here, we analyzed the presence of Stau1 in stress granules induced in transformed and non-transformed cell lines of distinct origin. Using a specific antibody against Stau1 (Craig et al., 2005), we found that this molecule was present in stress granules induced in NIH 3T3, HeLa, BHK, COS-7, WI-38, H1299 and U2OS cells, upon exposure to the calcium-pump inhibitor thapsigargin -a known inductor of endoplasmic reticulum stress -as well as in stress granules induced by arsenite, which induces oxidative stress ( Fig. 1 and M.G.T., L.J.M.T. and G.L.B., unpublished data). Stau1 was observed to localize in every stress granule identified by...
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