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Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation.

Zhao R, Kakihara Y, Gribun A, Huen J, Yang G, Khanna M, Costanzo M, Brost RL, Boone C, Hughes TR, Yip CM, Houry WA - J. Cell Biol. (2008)

Bottom Line: Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein.As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions.Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT
Hsp90 is a highly conserved molecular chaperone that is involved in modulating a multitude of cellular processes. In this study, we identify a function for the chaperone in RNA processing and maintenance. This functionality of Hsp90 involves two recently identified interactors of the chaperone: Tah1 and Pih1/Nop17. Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein. Tah1 and Pih1 bind to the essential helicases Rvb1 and Rvb2 to form the R2TP complex, which we demonstrate is required for the correct accumulation of box C/D small nucleolar ribonucleoproteins. Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs.

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A model of Hsp90 and R2TP function in the modulation of snoRNP assembly. In vivo, Pih1 is degraded in the absence of Hsp90/Tah1, whereas in vitro, Pih1 can misfold and form large soluble aggregates. Hsp90 and Tah1 bind and stabilize Pih1, probably resulting in a transient formation of an Hsp90–Tah1–Pih1 complex. Hsp90, Tah1, and Pih1 associate with the Rvb1/2 complex, resulting in formation of the R2TP complex and Hsp90, both of which are then involved in proper assembly/maintenance of box C/D snoRNPs. Hsp90, Tah1, Pih1, and Rvb1/2 are proposed to also affect the accumulation of other noncoding RNAs (not depicted).
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fig8: A model of Hsp90 and R2TP function in the modulation of snoRNP assembly. In vivo, Pih1 is degraded in the absence of Hsp90/Tah1, whereas in vitro, Pih1 can misfold and form large soluble aggregates. Hsp90 and Tah1 bind and stabilize Pih1, probably resulting in a transient formation of an Hsp90–Tah1–Pih1 complex. Hsp90, Tah1, and Pih1 associate with the Rvb1/2 complex, resulting in formation of the R2TP complex and Hsp90, both of which are then involved in proper assembly/maintenance of box C/D snoRNPs. Hsp90, Tah1, Pih1, and Rvb1/2 are proposed to also affect the accumulation of other noncoding RNAs (not depicted).

Mentions: Based on our data, the R2P complex functions in the proper assembly of the box C/D core protein complex composed of Nop1, Nop56, Nop58, and Snu13. Several of our experiments support this conclusion. (1) SGA array indicated that RVB1, RVB2, and PIH1 have many genetic interactions, suggesting that they are involved in a variety of cellular functions. However, all three genes genetically interact with NOP58 (Fig. 5, A and B). (2) Cells deleted or depleted of Rvb1, Rvb2, or Pih1 have a reduced accumulation of box C/D snoRNAs in log and stationary phases (Fig. 6, C and D). (3) The box C/D core protein complex is destabilized in rvb1, rvb2, and pih1 mutant backgrounds as indicated by enhanced binding of Hsp90 to this complex (Figs. 7 C and S5 B) under stationary-phase growth conditions. Our observation of the binding of Hsp90 to the box C/D core protein complex has not been reported before and further implicates Hsp90 in playing a role in rRNA biogenesis or maintenance. This role of Hsp90 is most evident under stress conditions such as heat shock or in stationary phase. Thus, the chaperone might either be required for the biogenesis of snoRNA or for the maintenance of snoRNA under these stress conditions. This effect of Hsp90 partly results from its effect on the stability of Pih1 (Fig. 8).


Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation.

Zhao R, Kakihara Y, Gribun A, Huen J, Yang G, Khanna M, Costanzo M, Brost RL, Boone C, Hughes TR, Yip CM, Houry WA - J. Cell Biol. (2008)

A model of Hsp90 and R2TP function in the modulation of snoRNP assembly. In vivo, Pih1 is degraded in the absence of Hsp90/Tah1, whereas in vitro, Pih1 can misfold and form large soluble aggregates. Hsp90 and Tah1 bind and stabilize Pih1, probably resulting in a transient formation of an Hsp90–Tah1–Pih1 complex. Hsp90, Tah1, and Pih1 associate with the Rvb1/2 complex, resulting in formation of the R2TP complex and Hsp90, both of which are then involved in proper assembly/maintenance of box C/D snoRNPs. Hsp90, Tah1, Pih1, and Rvb1/2 are proposed to also affect the accumulation of other noncoding RNAs (not depicted).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2234237&req=5

fig8: A model of Hsp90 and R2TP function in the modulation of snoRNP assembly. In vivo, Pih1 is degraded in the absence of Hsp90/Tah1, whereas in vitro, Pih1 can misfold and form large soluble aggregates. Hsp90 and Tah1 bind and stabilize Pih1, probably resulting in a transient formation of an Hsp90–Tah1–Pih1 complex. Hsp90, Tah1, and Pih1 associate with the Rvb1/2 complex, resulting in formation of the R2TP complex and Hsp90, both of which are then involved in proper assembly/maintenance of box C/D snoRNPs. Hsp90, Tah1, Pih1, and Rvb1/2 are proposed to also affect the accumulation of other noncoding RNAs (not depicted).
Mentions: Based on our data, the R2P complex functions in the proper assembly of the box C/D core protein complex composed of Nop1, Nop56, Nop58, and Snu13. Several of our experiments support this conclusion. (1) SGA array indicated that RVB1, RVB2, and PIH1 have many genetic interactions, suggesting that they are involved in a variety of cellular functions. However, all three genes genetically interact with NOP58 (Fig. 5, A and B). (2) Cells deleted or depleted of Rvb1, Rvb2, or Pih1 have a reduced accumulation of box C/D snoRNAs in log and stationary phases (Fig. 6, C and D). (3) The box C/D core protein complex is destabilized in rvb1, rvb2, and pih1 mutant backgrounds as indicated by enhanced binding of Hsp90 to this complex (Figs. 7 C and S5 B) under stationary-phase growth conditions. Our observation of the binding of Hsp90 to the box C/D core protein complex has not been reported before and further implicates Hsp90 in playing a role in rRNA biogenesis or maintenance. This role of Hsp90 is most evident under stress conditions such as heat shock or in stationary phase. Thus, the chaperone might either be required for the biogenesis of snoRNA or for the maintenance of snoRNA under these stress conditions. This effect of Hsp90 partly results from its effect on the stability of Pih1 (Fig. 8).

Bottom Line: Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein.As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions.Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT
Hsp90 is a highly conserved molecular chaperone that is involved in modulating a multitude of cellular processes. In this study, we identify a function for the chaperone in RNA processing and maintenance. This functionality of Hsp90 involves two recently identified interactors of the chaperone: Tah1 and Pih1/Nop17. Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein. Tah1 and Pih1 bind to the essential helicases Rvb1 and Rvb2 to form the R2TP complex, which we demonstrate is required for the correct accumulation of box C/D small nucleolar ribonucleoproteins. Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs.

Show MeSH
Related in: MedlinePlus