1. Staufen1 is Essential for Cell-Cycle Transitions and Cell Proliferation Via the Control of E2F1 Expression
- Author
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Bellastrid Doran, Luc DesGroseillers, Florence Bonnet-Magnaval, Stevenson Ly, Diana Ioana Hotea, and Mehdi Ghram
- Subjects
Untranslated region ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,E2F1 ,Humans ,RNA, Messenger ,Molecular Biology ,Post-transcriptional regulation ,Transcription factor ,Telomerase ,030304 developmental biology ,Cell Proliferation ,Regulation of gene expression ,0303 health sciences ,Binding Sites ,Chemistry ,Cell growth ,RNA-Binding Proteins ,Cell Cycle Checkpoints ,Cell cycle ,Cell sorting ,Cell biology ,Cytoskeletal Proteins ,Gene Expression Regulation ,030217 neurology & neurosurgery ,E2F1 Transcription Factor ,HeLa Cells ,Transcription Factors - 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.
- Published
- 2020