Molecular Composition of Staufen2-Containing Ribonucleoproteins in Embryonic Rat Brain

Maher-Laporte, Marjolaine; Berthiaume, Frédéric; Moreau, Marielle; Julien, Louis-André; Lapointe, Gabriel; Mourez, Michaël; DesGroseillers, Luc

doi:10.1371/journal.pone.0011350

Cited by 26 publications

(23 citation statements)

References 57 publications

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“…Furthermore, STAU2 62 -HIS and STAU2 59 -HIS pulled down a comparable amount of GST-STAU1 55 , STAU2 62 -GST, or STAU2 59 -GST and, as expected, did not pull down GST-PABPC1 ( Fig. 3 B and C) (26). These findings indicate that the efficiencies with which each STAU2 isoform interacts with itself, with one another, or with STAU1 55 are indistinguishable in vitro ( Fig.…”

Section: Stau2 and Stau1 Paralogs Self-associate And Associate With Onesupporting

confidence: 73%

Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity

Park

Gleghorn

Maquat

2012

Proc. Natl. Acad. Sci. U.S.A.

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Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3′-untranslated regions (3′ UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing. Compared with STAU1, STAU2 binds ∼10-fold more UPF1 and ∼two-to fivefold more of those SBS-containing mRNAs that were tested, and it comparably promotes UPF1 helicase activity, which is critical for SMD. STAU1-or STAU2-mediated augmentation of UPF1 helicase activity is not accompanied by enhanced ATP hydrolysis but does depend on ATP binding and a basal level of UPF1 ATPase activity. Studies of STAU2 demonstrate it changes the conformation of RNA-bound UPF1. These findings, and evidence for STAU1−STAU1, STAU2−STAU2, and STAU1−STAU2 formation in vitro and in cells, are consistent with results from tethering assays: the decrease in mRNA abundance brought about by tethering siRNA-resistant STAU2 or STAU1 to an mRNA 3′ UTR is inhibited by downregulating the abundance of cellular STAU2, STAU1, or UPF1. It follows that the efficiency of SMD in different cell types reflects the cumulative abundance of STAU1 and STAU2. We propose that STAU paralogs contribute to SMD by "greasing the wheels" of RNA-bound UPF1 so as to enhance its unwinding capacity per molecule of ATP hydrolyzed.protein-protein interactions | protein-RNA interactions M ammalian cells contain two Staufen (STAU) paralogs, STAU1 and STAU2. Each derives from a separate gene that produces multiple protein isoforms via alternative pre-mRNA splicing and/or polyadenylation. Every STAU1 and STAU2 isoform contains multiple conserved dsRNA-binding domains (RBDs), of which dsRBD3 and dsRBD4 constitute the major if not sole active dsRNA-binding sites (1, 2).Although STAU1 and probably STAU2 are expressed ubiquitously, STAU2 is most abundant in heart and brain (1, 3). Both paralogs are present in ribonucleoprotein particles (RNPs) within neuronal cell bodies and dendrites (1, 4-7). Both are also involved in the microtubule-dependent transport of RNAs to dendrites of polarized neurons (5, 8), presumably via the tubulinbinding domain (2). Moreover, both paralogs play a crucial role in the formation and maintenance of the dendritic spines of hippocampal neurons and are required for synaptic plasticity and memory (7, 9-11), although the detection of paralog-specific RNA granules in the distal dendrites of rat hippocampal neurons has been used to argue for paralog-distinct functions (1). Additional support for paralog-specific roles derives from the demonstration using rat hippocampal slice cultures that STAU1 but not STAU2 functions in the late phase of forskolin-induced longterm potentiation (10-12), whereas STAU2 but not STAU1 is involved in metabotropic ...

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Section: Stau2 and Stau1 Paralogs Self-associate And Associate With Onesupporting

confidence: 73%

Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity

Park

Gleghorn

Maquat

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…By first elucidating the YB-1 interactome in liver cells permissive to HCV infection, we found mostly RNA-binding proteins. This was not surprising, considering that YB-1 is frequently found in MS analyses of RNPs (63)(64)(65)(66)(67)(68). We then challenged the YB-1 partner hits for a potential role in vRNA replication in HCV replicon-containing cells.…”

Section: Discussionmentioning

confidence: 96%

A Host YB-1 Ribonucleoprotein Complex Is Hijacked by Hepatitis C Virus for the Control of NS3-Dependent Particle Production

Chatel‐Chaix

Germain

Motorina

et al. 2013

J Virol

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dHepatitis C virus (HCV) orchestrates the different stages of its life cycle in time and space through the sequential participation of HCV proteins and cellular machineries; hence, these represent tractable molecular host targets for HCV elimination by combination therapies. We recently identified multifunctional Y-box-binding protein 1 (YB-1 or YBX1) as an interacting partner of NS3/4A protein and HCV genomic RNA that negatively regulates the equilibrium between viral translation/replication and particle production. To identify novel host factors that regulate the production of infectious particles, we elucidated the YB-1 interactome in human hepatoma cells by a quantitative mass spectrometry approach. We identified 71 YB-1-associated proteins that included previously reported HCV regulators DDX3, heterogeneous nuclear RNP A1, and ILF2. Of the potential YB-1 interactors, 26 proteins significantly modulated HCV replication in a gene-silencing screening. Following extensive interaction and functional validation, we identified three YB-1 partners, C1QBP, LARP-1, and IGF2BP2, that redistribute to the surface of corecontaining lipid droplets in HCV JFH-1-expressing cells, similarly to YB-1 and DDX6. Importantly, knockdown of these proteins stimulated the release and/or egress of HCV particles without affecting virus assembly, suggesting a functional YB-1 protein complex that negatively regulates virus production. Furthermore, a JFH-1 strain with the NS3 Q221L mutation, which promotes virus production, was less sensitive to this negative regulation, suggesting that this HCV-specific YB-1 protein complex modulates an NS3-dependent step in virus production. Overall, our data support a model in which HCV hijacks host cell machinery containing numerous RNA-binding proteins to control the equilibrium between viral RNA replication and NS3-dependent late steps in particle production.

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“…89 An identification of the interactors of staufen2 also identified ribosomal proteins and cytoskeletal components. 90 Fritzsche and colleagues analyzed the interacting partners of two proteins, barentsz and staufen2, finding several proteins in common between the two but also a large number of differences, implying that the composition of different localization RNP particles may be more diverse than expected. 91 Several translational repressors were found in both complexes, consistent with the idea that transported RNA molecules are translationally repressed while they are in transit.…”

Section: Identification Of Trans Factorsmentioning

confidence: 99%

Genomic analysis of RNA localization

2014

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The localization of mRNAs to specific subcellular sites is widespread, allowing cells to spatially restrict and regulate protein production, and playing important roles in development and cellular physiology. This process has been studied in mechanistic detail for several RNAs. However, the generality or specificity of RNA localization systems and mechanisms that impact the many thousands of localized mRNAs has been difficult to assess. In this review, we discuss the current state of the field in determining which RNAs localize, which RNA sequences mediate localization, the protein factors involved, and the biological implications of localization. For each question, we examine prominent systems and techniques that are used to study individual messages, highlight recent genome-wide studies of RNA localization, and discuss the potential for adapting other high-throughput approaches to the study of localization.

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Molecular Composition of Staufen2-Containing Ribonucleoproteins in Embryonic Rat Brain

Cited by 26 publications

References 57 publications

Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity

Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity

A Host YB-1 Ribonucleoprotein Complex Is Hijacked by Hepatitis C Virus for the Control of NS3-Dependent Particle Production

Genomic analysis of RNA localization

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