Mammalian Staufen 1 is recruited to stress granules and impairs their assembly

Thomas, María Gabriela; Tosar, Leandro Julián Martínez; Desbats, María Andrea; Leishman, Claudia C.; Boccaccio, Graciela Lidia

doi:10.1242/jcs.038208

Cited by 123 publications

(162 citation statements)

References 62 publications

(104 reference statements)

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“…As reported previously, we found that TIA1 and TIAR have a nuclear localization under resting conditions, and that, shortly after stress induction, numerous small aggregates containing TIA1, TIAR and eIF3 begin to form in the cytoplasm (supplementary material Fig. S1A,B) (reviewed by Anderson and Kedersha, 2006;Anderson and Kedersha, 2008;Thomas et al, 2009). Soon afterwards, these particles collapsed into larger granules (supplementary material Fig.…”

Section: Retrograde Transport Mediated By Dhc1 and Bicd1 Is Required supporting

confidence: 73%

“…PBs are present in resting cells and they are further induced upon stress. SGs grow in close contact with PBs, suggesting that an active flow of mRNAs and proteins occurs between the two types of foci (reviewed by Anderson and Kedersha, 2008;Ohn et al, 2008;Mollet et al, 2008;Thomas et al, 2009). Both PBs and SGs are in equilibrium with translating polysomes.…”

Section: Introductionmentioning

confidence: 99%

“…The foci dissolve with distinct kinetics when polysomes are pharmacologically stabilized (Brengues et al, 2005;Eulalio et al, 2007b;Kedersha et al, 2005;Sivan et al, 2007) (reviewed by Anderson and Kedersha, 2008;Franks and Lykke-Andersen, 2008). The equilibrium between SGs and polysomes is regulated by Staufen 1, a double-stranded RNAbinding protein that is present in both structures and that apparently stabilizes polysomes (Thomas et al, 2009). SGs and PBs are highly dynamic, and fluorescence recovery after photobleaching (FRAP) analysis has revealed a rapid exchange of mRNAs and proteins with the cytosol (Kedersha et al, 2005;Leung et al, 2006;Aizer et al, 2008;Mollet et al, 2008) (reviewed by Anderson and Kedersha, 2006;Anderson and Kedersha, 2008;Franks and Lykke-Andersen, 2008), thus suggesting that an active transport in and out of the foci, presumably mediated by molecular motors, takes place.…”

Section: Introductionmentioning

confidence: 99%

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Dynein and kinesin regulate stress-granule and P-body dynamics

Loschi

Leishman

Berardone

et al. 2009

Journal of Cell Science

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162

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Stress granules (SGs) and P-bodies (PBs) are related cytoplasmic structures harboring silenced mRNAs. SGs assemble transiently upon cellular stress, whereas PBs are constitutive and are further induced by stress. Both foci are highly dynamic, with messenger ribonucleoproteins (mRNPs) and proteins rapidly shuttling in and out. Here, we show that impairment of retrograde transport by knockdown of mammalian dynein heavy chain 1 (DHC1) or bicaudal D1 (BicD1) inhibits SG formation and PB growth upon stress, without affecting protein-synthesis blockage. Conversely, impairment of anterograde transport by knockdown of kinesin-1 heavy chain (KIF5B) or kinesin light chain 1 (KLC1) delayed SG dissolution. Strikingly, SG dissolution is not required to restore translation. Simultaneous knockdown of dynein and kinesin reverted the effect of single knockdowns on both SGs and PBs, suggesting that a balance between opposing movements driven by these molecular motors governs foci formation and dissolution. Finally, we found that regulation of SG dynamics by dynein and kinesin is conserved in Drosophila.

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Section: Retrograde Transport Mediated By Dhc1 and Bicd1 Is Required supporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynein and kinesin regulate stress-granule and P-body dynamics

Loschi

Leishman

Berardone

et al. 2009

Journal of Cell Science

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162

229

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“…Stress granules form during the translational silencing triggered by cellular stress, and XRN1 is recruited to stress granules under specific conditions (Thomas et al, 2009;Thomas et al, 2011). To investigate whether the XRN1 puncta induced concomitantly with the translational silencing triggered by NMDA are stress granules, we assessed the presence of the eukaryotic translation factor 3g (eIF3g, also known as EIF3B), a widely accepted stress granule marker.…”

Section: Xrn1 Forms Synaptic Bodies That Are Different From Processinmentioning

confidence: 99%

Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Luchelli¹,

Thomas²,

Boccaccio³

2015

Journal of Cell Science

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Repression of mRNA translation is linked to the formation of specific cytosolic foci such as stress granules and processing bodies, which store or degrade mRNAs. In neurons, synaptic activity regulates translation at the post-synapse and this is important for plasticity. Nmethyl-D-aspartate (NMDA) receptor stimulation downregulates translation, and we speculate that this is linked to the formation of unknown mRNA-silencing foci. Here, we show that the 59-39 exoribonuclease XRN1 forms discrete clusters associated with the post-synapse that are different from processing bodies or stress granules, and we named them synaptic XRN1 bodies (SX-bodies). Using primary neurons, we found that the SX-bodies respond to synapse stimulation and that their formation correlates inversely with the local translation rate. SX-bodies increase in size and number upon NMDA stimulation, and metabotropic glutamate receptor activation provokes SX-body dissolution, along with increased translation. The response is specific and the previously described Smaug1 foci and FMRP granules show a different response. Finally, XRN1 knockdown impairs the translational repression triggered by NMDA. Collectively, these observations support a role for the SX-bodies in the reversible masking and silencing of mRNAs at the synapse.

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“…In flies, 3′ UTR-bound Staufen is required for proper localization and translational control of bicoid and prospero mRNAs during oogenesis 4,5 . In mammals, Stau1 has been implicated in mRNA transport to neuronal dendrites 6 , regulation of translation via physical interaction with the ribosome 7 , a form of translation-dependent mRNA degradation known as Staufen-mediated decay (SMD) [8][9][10][11] , regulation of stress-granule homeostasis 12 , alternative splicing, nuclear export and translation of a gene containing 3′-UTR CUG-repeat expansions 13 . Although Stau1 is not essential for mammalian development, neurons lacking Stau1 have dendritic spinemorphogenesis defects in vitro, and knockout mice have locomotor-activity deficits 14 .…”

mentioning

confidence: 99%

Staufen1 senses overall transcript secondary structure to regulate translation

Ricci

Küçükural

Cenik

et al. 2013

Nat Struct Mol Biol

122

184

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Human Staufen1 (Stau1) is a double-stranded RNA (dsRNA)-binding protein implicated in multiple post-transcriptional gene-regulatory processes. Here we combined RNA immunoprecipitation in tandem (RIPiT) with RNase footprinting, formaldehyde cross-linking, sonication-mediated RNA fragmentation and deep sequencing to map Staufen1-binding sites transcriptome wide. We find that Stau1 binds complex secondary structures containing multiple short helices, many of which are formed by inverted Alu elements in annotated 3′ untranslated regions (UTRs) or in 'strongly distal' 3′ UTRs. Stau1 also interacts with actively translating ribosomes and with mRNA coding sequences (CDSs) and 3′ UTRs in proportion to their GC content and propensity to form internal secondary structure. On mRNAs with high CDS GC content, higher Stau1 levels lead to greater ribosome densities, thus suggesting a general role for Stau1 in modulating translation elongation through structured CDS regions. Our results also indicate that Stau1 regulates translation of transcription-regulatory proteins.Staufen proteins are highly conserved dsRNA-binding proteins (dsRBPs) found in most bilateral animals 1 . Mammals contain two Staufen paralogs encoded by different loci. Stau1, Reprints and permissions information is available online at

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Mammalian Staufen 1 is recruited to stress granules and impairs their assembly

Cited by 123 publications

References 62 publications

Dynein and kinesin regulate stress-granule and P-body dynamics

Dynein and kinesin regulate stress-granule and P-body dynamics

Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Staufen1 senses overall transcript secondary structure to regulate translation

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