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The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery

¹ Institute of Molecular Genetics of Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, Montpellier Cedex 5, France
² Maturation des ARN et Enzymologie Moléculaire, Unité Mixte de Recherche 7567, Centre National de la Recherche Scientifique, Université Henri Poincaré, Nancy Université, Faculté des Sciences et Techniques, 54506 Vandoeuvre-les-Nancy, France
³ Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France
⁴ Laboratoire de Biologie Moléculaire Eucaryote, Université Paul Sabatier, 31062 Toulouse, France
⁵ Institute of Genetics and Molecular and Cellular Biology, 67404 Illkirch, France

Correspondence to Christine Allmang: c.allmang{at}ibmc.u-strasbg.fr; Edouard Bertrand: Edouard.Bertrand{at}igmm.cnrs.fr; or Bruno Charpentier: Bruno.Charpentier{at}maem.uhp-nancy.fr

RNA-binding proteins of the L7Ae family are at the heart of many essential ribonucleoproteins (RNPs), including box C/D and H/ACA small nucleolar RNPs, U4 small nuclear RNP, telomerase, and messenger RNPs coding for selenoproteins. In this study, we show that Nufip and its yeast homologue Rsa1 are key components of the machinery that assembles these RNPs. We observed that Rsa1 and Nufip bind several L7Ae proteins and tether them to other core proteins in the immature particles. Surprisingly, Rsa1 and Nufip also link assembling RNPs with the AAA + adenosine triphosphatases hRvb1 and hRvb2 and with the Hsp90 chaperone through two conserved adaptors, Tah1/hSpagh and Pih1. Inhibition of Hsp90 in human cells prevents the accumulation of U3, U4, and telomerase RNAs and decreases the levels of newly synthesized hNop58, hNHP2, 15.5K, and SBP2. Thus, Hsp90 may control the folding of these proteins during the formation of new RNPs. This suggests that Hsp90 functions as a master regulator of cell proliferation by allowing simultaneous control of cell signaling and cell growth.

Abbreviations used in this paper: IP, immunoprecipitation; mRNP, messenger RNP; qPCR, quantitative PCR; scaRNP, small Cajal body RNP; SECIS, selenocysteine insertion sequence; snoRNA, small nucleolar RNA; snoRNP, small nucleolar RNP; snRNA, small nuclear RNA; snRNP, small nuclear RNP; TPR, tetratricopeptide repeat; Y2H, yeast two hybrid; Y3H, yeast three hybrid.

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