Staufen1 is Essential for Cell-Cycle Transitions and Cell Proliferation Via the Control of E2F1 Expression. Issue 13 (12th June 2020)

• Record Type: Journal Article
• Authors: Ghram, Mehdi; Bonnet-Magnaval, Florence; Hotea, Diana Ioana; Doran, Bellastrid; Ly, Stevenson; DesGroseillers, Luc
• Is Part Of: Journal of molecular biology. Volume 432:Issue 13(2020)
• Page Start: 3881
• Page End: 3897
• Publication Date: 2020-06-12
• Subjects: STAU1 Staufen1 -- 3′UTR 3′ untranslated region -- SMD STAU1-mediatedRNA decay -- FACS fluorescence-activated cell sorting -- FUCCI fluorescent ubiquitination-based cell-cycle indicator -- siRNA small interfering RNA -- shRNA short hairpin RNA -- R-Luc renilla luciferase -- F-Luc firefly luciferase -- WT cells wild-type cells -- KD cells knockdown cells; Staufen1 -- E2F1 -- cell cycle -- post-transcriptional regulation -- RNA regulon; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.04.016
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Cell cycle is a highly regulated process that is finely coordinated by a plethora of interconnected regulators. In this paper, we report that post-transcriptional mechanisms mediated by the RNA-binding protein Staufen1 (STAU1) are essential for the proliferation of non-transformed cells (hTERT-RPE1 and IMR90). Cell sorting quantification and time-lapse video microscopy using FUCCI-hTERT-RPE1 cells identified the G1 /S and G2 /M phase transitions of the cell cycle as crucial steps for STAU1 functions. The level of expression of 35 transcripts coding for cell-cycle regulators is up- or down-regulated following STAU1 depletion. Among others, expression of E2F1, a transcription factor essential for the G1 /S transition, is decreased in STAU1 depleted cells, dependent on a STAU1-binding site in the 3′ untranslated region of E2F1 mRNA. Interestingly, E2F1, in turn, increases STAU1 transcription, highlighting a regulatory loop that enhances expression of both STAU1 and E2F1. Our results indicate that a STAU1-mediatedpost-transcriptional mechanism of gene regulation controls an mRNA regulon involved in decision making during cell-cycle phase transitions and that this mechanism is essential for cell-cycle progression in non-tumor cells. Graphical abstract: Unlabelled Image Highlights: Staufen1 depletion impairs cell proliferation in non-transformed cells. Staufen1 facilitates cell-cycle transitions. Staufen1 enhances E2F1 expression by binding to its 3′UTR mRNA. E2F1 enhances Staufen1 transcription.