Staufen1 is Essential for Cell-Cycle Transitions and Cell Proliferation Via the Control of E2F1 Expression.
J Mol Biol
; 432(13): 3881-3897, 2020 06 12.
Article
em En
| MEDLINE
| ID: mdl-32335035
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
/
Telomerase
/
Proteínas do Citoesqueleto
/
Fator de Transcrição E2F1
/
Pontos de Checagem do Ciclo Celular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2020
Tipo de documento:
Article