The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.
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.
Boulon
Séverine
S
Institute of Molecular Genetics of Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, Montpellier Cedex 5, France.
Marmier-Gourrier
Nathalie
N
Pradet-Balade
Bérengère
B
Wurth
Laurence
L
Verheggen
Céline
C
Jády
Beáta E
BE
Rothé
Benjamin
B
Pescia
Christina
C
Robert
Marie-Cécile
MC
Kiss
Tamás
T
Bardoni
Barbara
B
Krol
Alain
A
Branlant
Christiane
C
Allmang
Christine
C
Bertrand
Edouard
E
Charpentier
Bruno
B
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
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