Assembly principles of the human R2TP chaperone complex reveal the presence of R2T and R2P complexes

Seraphim, Thiago Vargas; Nano, Nardin; Cheung, Yiu Wing Sunny; Aluksanasuwan, Siripat; Colleti, Carolina; Mao, Yu-Qian; Bhandari, Vaibhav; Young, Gavin; Höll, Larissa; Phanse, Sadhna; Gordiyenko, Yuliya; Southworth, Daniel R.; Robinson, Carol V.; Thongboonkerd, Visith; Gava, Lisandra M.; Borges, Júlio César; Babu, Mohan; Barbosa, Leandro R.S.; Ramos, Carlos Henrique Inácio; Kukura, Philipp; Houry, Walid

doi:10.1016/j.str.2021.08.002

Cited by 19 publications

(34 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rvb1/Rvb2 were initially found to be associated with many chromatin-remodeling and transcription related complexes. This has further been expanded on and several studies have demonstrated a chaperone-like activity in the formation of various complexes including the assembly of chromatin remodeling complexes and RNA polymerase II (20–22). It may be that recruiting Rvb1/Rvb2 to the nascent RNA increases the local concentration, driving further enhancement of transcription-related processes.…”

Section: Discussionmentioning

confidence: 99%

“…Structural studies have shown that they form a dodecamer comprised of a stacked Rvb1 hexametric ring and a Rvb2 hexametric ring. They were reported as the chaperones of multiprotein complexes involved in chromatin remodeling processes and other nuclear pathways including snoRNP assembly (17)(18)(19)(20)(21)(22)(23). These two proteins are generally thought to act on DNA but have been found to be core components of mammalian and yeast cytoplasmic stress granules (24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

Chen

Tracy

Harjono

et al. 2021

Preprint

View full text Add to dashboard Cite

During times of unpredictable stress, organisms must adapt their gene expression to maximize survival. Along with changes in transcription, one conserved means of gene regulation during conditions that quickly represses translation is the formation of cytoplasmic phase-separated mRNP granules such as P-bodies and stress granules. Previously, we identified that distinct steps in gene expression can be coupled during glucose starvation as promoter sequences in the nucleus are able to direct the subcellular localization and translatability of mRNAs in the cytosol. Here, we report that Rvb1 and Rvb2, conserved ATPase proteins implicated as protein assembly chaperones and chromatin remodelers, were enriched at the promoters and mRNAs of genes involved in alternative glucose metabolism pathways that we previously found to be transcriptionally upregulated but translationally downregulated during glucose starvation in yeast. Engineered Rvb1/Rvb2-binding on mRNAs was sufficient to sequester the mRNAs into phase-separated granules and repress their translation. Additionally, this Rvb-tethering to the mRNA drove further transcriptional upregulation of the target genes. Overall, our results point to Rvb1/Rvb2 coupling transcription, mRNA granular localization, and translatability of mRNAs during glucose starvation. This Rvb-mediated rapid gene regulation could potentially serve as an efficient recovery plan for cells after stress removal.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

Chen

Tracy

Harjono

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Within the PAQosome, RPAP3 and PIH1D1 are proposed to function as scaffolds for Hsp90 and its diverse client proteins. RPAP3 contains an RPAP3_N domain that mediates interactions with substrates enriched with helical-type domains [ 22 ]; two TPR domains, whereby TPR2 has high affinity for Hsp90 [ 23 ]; an intrinsically disordered region that makes contacts with RUVBL1 [ 22 ]; and an RPAP3_C domain that binds to the ATPase side of RUVBL2 [ 24 ]. PIH1D1 contains an N-terminal PIH1 domain that binds DpSDD/E motifs on clients [ 25 , 26 ] and a C-terminal CHORD and Sgt1 (CS) domain that binds RPAP3 [ 24 , 27 ].…”

Section: Overview Of Hsp90 Structure and Its Function With R2tpmentioning

confidence: 99%

“…PIH1D1 contains an N-terminal PIH1 domain that binds DpSDD/E motifs on clients [ 25 , 26 ] and a C-terminal CHORD and Sgt1 (CS) domain that binds RPAP3 [ 24 , 27 ]. Although it has been proposed that PIH1D1 binds to and regulates RUVBL2 ATPase activity as a nucleotide exchange factor, our group has shown that, within the R2TP complex, PIH1D1 binds exclusively to RPAP3 and that PIH1D1 has little effect on RUVBL1/2 ATPase activity and nucleotide binding affinity [ 22 ]. Interestingly, although our model suggests that PIH1D1 only interacts with RPAP3 within the R2TP complex, we have identified R2T and R2P complexes in vitro and in cellulo [ 22 ].…”

Section: Overview Of Hsp90 Structure and Its Function With R2tpmentioning

confidence: 99%

“…Although it has been proposed that PIH1D1 binds to and regulates RUVBL2 ATPase activity as a nucleotide exchange factor, our group has shown that, within the R2TP complex, PIH1D1 binds exclusively to RPAP3 and that PIH1D1 has little effect on RUVBL1/2 ATPase activity and nucleotide binding affinity [ 22 ]. Interestingly, although our model suggests that PIH1D1 only interacts with RPAP3 within the R2TP complex, we have identified R2T and R2P complexes in vitro and in cellulo [ 22 ]. The significance of these findings in regard to Hsp90 function has yet to be determined.…”

Section: Overview Of Hsp90 Structure and Its Function With R2tpmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization

Lynham

Houry

2022

Biomolecules

Self Cite

View full text Add to dashboard Cite

Hsp90 is a ubiquitous molecular chaperone involved in many cell signaling pathways, and its interactions with specific chaperones and cochaperones determines which client proteins to fold. Hsp90 has been shown to be involved in the promotion and maintenance of proper protein complex assembly either alone or in association with other chaperones such as the R2TP chaperone complex. Hsp90-R2TP acts through several mechanisms, such as by controlling the transcription of protein complex subunits, stabilizing protein subcomplexes before their incorporation into the entire complex, and by recruiting adaptors that facilitate complex assembly. Despite its many roles in protein complex assembly, detailed mechanisms of how Hsp90-R2TP assembles protein complexes have yet to be determined, with most findings restricted to proteomic analyses and in vitro interactions. This review will discuss our current understanding of the function of Hsp90-R2TP in the assembly, stabilization, and activity of the following seven classes of protein complexes: L7Ae snoRNPs, spliceosome snRNPs, RNA polymerases, PIKKs, MRN, TSC, and axonemal dynein arms.

show abstract

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8–9, 2022

Oosten-Hawle

Backe

Ben‐Zvi

et al. 2023

Cell Stress and Chaperones

View full text Add to dashboard Cite

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8–9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of the meeting here and recognize those that received recognition from the CSSI.

show abstract

Assembly principles of the human R2TP chaperone complex reveal the presence of R2T and R2P complexes

Cited by 19 publications

References 70 publications

Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation

The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8–9, 2022

Contact Info

Product

Resources

About