title: RNA content in the nucleolus alters p53 acetylation via MYBBP1A.
abstract: A number of external and internal insults disrupt nucleolar structure, and the resulting nucleolar stress stabilizes and activates p53. We show here that nucleolar disruption induces acetylation and accumulation of p53 without phosphorylation. We identified three nucleolar proteins, MYBBP1A, RPL5, and RPL11, involved in p53 acetylation and accumulation. MYBBP1A was tethered to the nucleolus through nucleolar RNA. When rRNA transcription was suppressed by nucleolar stress, MYBBP1A translocated to the nucleoplasm and facilitated p53-p300 interaction to enhance p53 acetylation. We also found that RPL5 and RPL11 were required for rRNA export from the nucleolus. Depletion of RPL5 or RPL11 blocked rRNA export and counteracted reduction of nucleolar RNA levels caused by inhibition of rRNA transcription. As a result, RPL5 or RPL11 depletion inhibited MYBBP1A translocation and p53 activation. Our observations indicated that a dynamic equilibrium between RNA generation and export regulated nucleolar RNA content. Perturbation of this balance by nucleolar stress altered the nucleolar RNA content and modulated p53 activity.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Akiko
authors.initials: A
authors.lastname: Murayama
authors.forename: Naohiro
authors.initials: N
authors.lastname: Katagiri
authors.forename: Yu-mi
authors.initials: YM
authors.lastname: Ohta
authors.forename: Etsuko
authors.initials: E
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masumoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ema
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D000107:Acetylation; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry*; D004268:DNA-Binding Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000032:analysis*; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000378:metabolism; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; C549166:ribosomal protein L5, human