HSP90 and Its R2TP/Prefoldin-like Cochaperone Are Involved in the Cytoplasmic Assembly of RNA Polymerase II

Boulon, Séverine; Pradet‐Balade, Bérengère; Verheggen, Céline; Molle, Dorothée; Boireau, Stéphanie; Georgieva, Marya; Azzag, Karim; Robert, Marie Cécile; Ahmad, Yasmeen; Neel, H. Bryan; Lamond, Angus I.; Bertrand, Édouard

doi:10.1016/j.molcel.2010.08.023

Cited by 252 publications

(377 citation statements)

References 45 publications

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“…In yeast, Pih1 targets R2TP to Nop58 (a core factor in box C/D snoRNP) (16). In mammals, PIH1D1 targets R2TP to dyskerin (yeast Cbf5 homologue, a core factor in box H/ACA snoRNP) (17), Rpb1 (a core subunit in RNA polymerase II) (18), and Tel2 [a core subunit in TTT (Tel2-Tti1-Tti2) complex] (19,20).…”

Section: Introductionmentioning

confidence: 99%

The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

Kakihara

Saeki

2014

Biomolecular Concepts

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R2TP was originally identified in yeast Saccharomyces cerevisiae as Hsp90 interacting complex, and is composed of four different proteins: Rvb1, Rvb2, Tah1, and Pih1. This complex is well-conserved in eukaryotes, and is involved in many cellular processes such as snoRNP biogenesis, RNA polymerase assembly, PIKK signaling, and apoptosis. An increasing number of research related to R2TP suggests a linkage of its function with tumorigenesis. In this review, we provide an overview of several recent studies on R2TP that are related to cell proliferation and carcinogenesis, and propose a possible role of R2TP in tumorigenesis through regulating snoRNA/snoRNP biogenesis.

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Section: Introductionmentioning

confidence: 99%

The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

Kakihara

Saeki

2014

Biomolecular Concepts

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“…Based on our data, a model for an Hsp90-Tah1-Pih1 ternary complex is proposed. 7 -containing protein associated with Hsp90) is a small protein of 111 amino acids (12.5 kDa). We discovered this previously uncharacterized protein during a proteomic screen for Hsp90 interactors (1).…”

mentioning

confidence: 99%

“…Rvb1 and Rvb2 are two highly conserved AAAϩ helicases involved in many different critical complexes in the cell (3,4). The R2TP complex is highly conserved from yeast to mammalian cells and has been shown to be required for the proper assembly of box C/D small nucleolar ribonucleoproteins (5,2), for the assembly of RNA polymerase II (6,7), and for the stability of the phosphatidylinositol 3-kinase-related kinases through binding to TEL2 (8). Furthermore, both human Pih1 (PIH1D1) and human Tah1 (RPAP3) have been shown to regulate apoptosis (9,10).…”

mentioning

confidence: 99%

Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90

Jiménez

Ugwu

Zhao

et al. 2012

Journal of Biological Chemistry

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Background: Tah1 and Pih1 are Hsp90 interactors that form a ternary complex with the chaperone. Results: NMR structure of Tah1 revealed the presence of two tetratricopeptide repeat motifs followed by a C helix and an unstructured region. Conclusion: Tah1 can bind simultaneously two other proteins using different interaction modes. Significance: The study provides important insights into protein complex assembly.

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“…Similar to the role of Tah1 in protecting Pih1, a small protein, Hit1, was also identified to interact with and protect Rsa1, thus revealing a complex regulatory network controlling snoRNP assembly in vivo (16). The human R2TP complex was also shown to aid in the assembly of RNA polymerase II complex (17). Human Pih1 homologue Pih1D1 interacts with phosphorylated Tel2 and recruits the R2TP complex in the assembly of PIKKs (phosphatidylinositol 3-kinase-related kinases) (18).…”

Section: The R2tpmentioning

confidence: 88%

The Proteasome Subunit Rpn8 Interacts with the Small Nucleolar RNA Protein (snoRNP) Assembly Protein Pih1 and Mediates Its Ubiquitin-independent Degradation in Saccharomyces cerevisiae

Paci

Liu

Zhang

et al. 2016

Journal of Biological Chemistry

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Pih1 is a scaffold protein of the Rvb1-Rvb2-Tah1-Pih1 (R2TP) protein complex, which is conserved in fungi and animals. The chaperone-like activity of the R2TP complex has been implicated in the assembly of multiple protein complexes, such as the small nucleolar RNA protein complex. However, the mechanism of the R2TP complex activity in vivo and the assembly of the complex itself are still largely unknown. Pih1 is an unstable protein and tends to aggregate when expressed alone. The C-terminal fragment of Pih1 contains multiple destabilization factors and acts as a degron when fused to other proteins. In this study, we investigated Pih1 interactors and identified a specific interaction between Pih1 and the proteasome subunit Rpn8 in yeast Saccharomyces cerevisiae when HSP90 co-chaperone Tah1 is depleted. By analyzing truncation mutants, we identified that the C-terminal 30 amino acids of Rpn8 are sufficient for the binding to Pih1 C terminus. With in vitro and in vivo degradation assays, we showed that the Pih1 C-terminal fragment Pih1(282-344) is able to induce a ubiquitin-independent degradation of GFP. Additionally, we demonstrated that truncation of the Rpn8 C-terminal disordered region does not affect proteasome assembly but specifically inhibits the degradation of the GFP-Pih1(282-344) fusion protein in vivo and Pih1 in vitro. We propose that Pih1 is a ubiquitin-independent proteasome substrate, and the direct interaction with Rpn8 C terminus mediates its proteasomal degradation. The R2TP2 complex, which is composed of Rvb1, Rvb2, Tah1, and Pih1, was first discovered in baking yeast (1) and is required for box C/D small nucleolar RNA protein (snoRNP) complex assembly and thus for the ribosomal RNA biogenesis (2). R2TP is a conserved protein complex and has also been identified in mammalian cells (3-5), fruit fly (6), plasmodium (7), and many other fungi species (8), whereas it is absent in higher plants (9). There are more than 70 different snoRNP complexes that are directly involved in ribosomal RNA processing, a critical step for ribosome assembly that requires a total of more than 200 assembly factors (10). The assembly of R2TP complex in vivo is also a highly dynamic process and is regulated by the molecular chaperone HSP90 and nutrition status (11). However, the mechanism by which R2TP controls box C/D snoRNP complex assembly is still largely unknown.Pih1, the scaffold protein within the R2TP complex, mediates the interaction between Tah1 and Rvb1-Rvb2 and subsequently controls the biogenesis of box C/D snoRNP (2, 3). Tah1 recruits HSP90 and protects Pih1 from degradation in vivo (12, 13). Pih1 interacts directly with Nop58, one of the core protein subunits in box C/D snoRNP (11) and affects its stability (14). Pih1 also interacts with Rsa1, another snoRNP assembly factor through which the R2TP complex may interact with the snoRNP core protein Snu13 (15). Similar to the role of Tah1 in protecting Pih1, a small protein, Hit1, was also identified to interact with and protect Rsa1, thus revealing a complex...

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HSP90 and Its R2TP/Prefoldin-like Cochaperone Are Involved in the Cytoplasmic Assembly of RNA Polymerase II

Cited by 252 publications

References 45 publications

The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90

The Proteasome Subunit Rpn8 Interacts with the Small Nucleolar RNA Protein (snoRNP) Assembly Protein Pih1 and Mediates Its Ubiquitin-independent Degradation in Saccharomyces cerevisiae

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