title: The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.
abstract: 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.
authors.affiliation: Institute of Molecular Genetics of Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, Montpellier Cedex 5, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Boulon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marmier-Gourrier
authors.forename: Bérengère
authors.initials: B
authors.lastname: Pradet-Balade
authors.forename: Laurence
authors.initials: L
authors.lastname: Wurth
authors.forename: Céline
authors.initials: C
authors.lastname: Verheggen
authors.forename: Beáta E
authors.initials: BE
authors.lastname: Jády
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rothé
authors.forename: Christina
authors.initials: C
authors.lastname: Pescia
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Robert
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: Alain
authors.initials: A
authors.lastname: Krol
authors.forename: Christiane
authors.initials: C
authors.lastname: Branlant
authors.forename: Christine
authors.initials: C
authors.lastname: Allmang
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Bruno
authors.initials: B
authors.lastname: Charpentier
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D017124:Conserved Sequence / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D018832:Molecular Chaperones; C403092:NUFIP1 protein, human; D009687:Nuclear Proteins; C497702:PIH1 protein, S cerevisiae; D016601:RNA-Binding Proteins; C402485:RSA1 protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C499592:TAH11 protein, S cerevisiae; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C428198:RVB1 protein, S cerevisiae; C428199:RVB2 protein, S cerevisiae; D004265:DNA Helicases