Drosophila spag is the homolog of RNA polymerase II-associated protein 3 (RPAP3) and recruits the heat shock proteins 70 and 90 (Hsp70 and Hsp90) during the assembly of cellular machineries

Nour El Houda Benbahouche, Ioannis Iliopoulos, István Török, Joachim Marhold, Julien Henri, Andrey V. Kajava, Robert Farkaš, Tore Kempf, Martina Schnölzer, Philippe Meyer, I. Kiss, Edouard Bertrand, Bernard M. Mechler, Bérengère Pradet-Balade

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The R2TP is a recently identified Hsp90 co-chaperone, composed of four proteins as follows: Pih1D1, RPAP3, and the AAA+-ATPases RUVBL1 and RUVBL2. In mammals, the R2TP is involved in the biogenesis of cellular machineries such as RNA polymerases, small nucleolar ribonucleoparticles and phosphatidylinositol 3-kinase-related kinases. Here, we characterize the spaghetti (spag) gene of Drosophila, the homolog of human RPAP3. This gene plays an essential function during Drosophila development. We show that Spag protein binds Drosophila orthologs of R2TP components and Hsp90, like its yeast counterpart. Unexpectedly, Spag also interacts and stimulates the chaperone activity of Hsp70. Using null mutants and flies with inducible RNAi, we show that spaghetti is necessary for the stabilization of snoRNP core proteins and target of rapamycin activity and likely the assembly of RNA polymerase II. This work highlights the strong conservation of both the HSP90/R2TP system and its clients and further shows that Spag, unlike Saccharomyces cerevisiae Tah1, performs essential functions in metazoans. Interaction of Spag with both Hsp70 and Hsp90 suggests a model whereby R2TP would accompany clients from Hsp70 to Hsp90 to facilitate their assembly into macromolecular complexes.

Original languageEnglish
Pages (from-to)6236-6247
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number9
DOIs
Publication statusPublished - Feb 28 2014

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HSP90 Heat-Shock Proteins
HSP70 Heat-Shock Proteins
RNA Polymerase II
Yeast
Drosophila
Small Nucleolar Ribonucleoproteins
Genes
TOR Serine-Threonine Kinases
Phosphatidylinositol 3-Kinase
Macromolecular Substances
Drosophila Proteins
Mammals
Essential Genes
DNA-Directed RNA Polymerases
RNA Interference
Diptera
Saccharomyces cerevisiae
Adenosine Triphosphatases
Conservation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Drosophila spag is the homolog of RNA polymerase II-associated protein 3 (RPAP3) and recruits the heat shock proteins 70 and 90 (Hsp70 and Hsp90) during the assembly of cellular machineries. / Benbahouche, Nour El Houda; Iliopoulos, Ioannis; Török, István; Marhold, Joachim; Henri, Julien; Kajava, Andrey V.; Farkaš, Robert; Kempf, Tore; Schnölzer, Martina; Meyer, Philippe; Kiss, I.; Bertrand, Edouard; Mechler, Bernard M.; Pradet-Balade, Bérengère.

In: Journal of Biological Chemistry, Vol. 289, No. 9, 28.02.2014, p. 6236-6247.

Research output: Contribution to journalArticle

Benbahouche, NEH, Iliopoulos, I, Török, I, Marhold, J, Henri, J, Kajava, AV, Farkaš, R, Kempf, T, Schnölzer, M, Meyer, P, Kiss, I, Bertrand, E, Mechler, BM & Pradet-Balade, B 2014, 'Drosophila spag is the homolog of RNA polymerase II-associated protein 3 (RPAP3) and recruits the heat shock proteins 70 and 90 (Hsp70 and Hsp90) during the assembly of cellular machineries', Journal of Biological Chemistry, vol. 289, no. 9, pp. 6236-6247. https://doi.org/10.1074/jbc.M113.499608
Benbahouche, Nour El Houda ; Iliopoulos, Ioannis ; Török, István ; Marhold, Joachim ; Henri, Julien ; Kajava, Andrey V. ; Farkaš, Robert ; Kempf, Tore ; Schnölzer, Martina ; Meyer, Philippe ; Kiss, I. ; Bertrand, Edouard ; Mechler, Bernard M. ; Pradet-Balade, Bérengère. / Drosophila spag is the homolog of RNA polymerase II-associated protein 3 (RPAP3) and recruits the heat shock proteins 70 and 90 (Hsp70 and Hsp90) during the assembly of cellular machineries. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 9. pp. 6236-6247.
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AU - Benbahouche, Nour El Houda

AU - Iliopoulos, Ioannis

AU - Török, István

AU - Marhold, Joachim

AU - Henri, Julien

AU - Kajava, Andrey V.

AU - Farkaš, Robert

AU - Kempf, Tore

AU - Schnölzer, Martina

AU - Meyer, Philippe

AU - Kiss, I.

AU - Bertrand, Edouard

AU - Mechler, Bernard M.

AU - Pradet-Balade, Bérengère

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