title: Cell cycle-dependent regulation of the RNA-binding protein Staufen1.
abstract: Staufen1 (Stau1) is a ribonucleic acid (RNA)-binding protein involved in the post-transcriptional regulation of gene expression. Recent studies indicate that Stau1-bound messenger RNAs (mRNAs) mainly code for proteins involved in transcription and cell cycle control. Consistently, we report here that Stau1 abundance fluctuates through the cell cycle in HCT116 and U2OS cells: it is high from the S phase to the onset of mitosis and rapidly decreases as cells transit through mitosis. Stau1 down-regulation is mediated by the ubiquitin-proteasome system and the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Stau1 interacts with the APC/C co-activators Cdh1 and Cdc20 via its first 88 N-terminal amino acids. The importance of controlling Stau155 levels is underscored by the observation that its overexpression affects mitosis entry and impairs proliferation of transformed cells. Microarray analyses identified 275 Stau1(55)-bound mRNAs in prometaphase cells, an early mitotic step that just precedes Stau1 degradation. Interestingly, several of these mRNAs are more abundant in Stau155-containing complexes in cells arrested in prometaphase than in asynchronous cells. Our results point out for the first time to the possibility that Stau1 participates in a mechanism of post-transcriptional regulation of gene expression that is linked to cell cycle progression in cancer cells.
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Boulay
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghram
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Wildriss
authors.initials: W
authors.lastname: Viranaicken
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Trépanier
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mollet
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Fréchina
authors.affiliation: Département de Biochimie, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit, Montréal, QC, H3T 1J4, Canada luc.desgroseillers@umontreal.ca.
authors.forename: Luc
authors.initials: L
authors.lastname: DesGroseillers
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D064199:Cdc20 Proteins / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008938:Mitosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex