Staufen1 localizes to the mitotic spindle and controls the localization of RNA populations to the spindle.

Staufen1 (STAU1) is an RNA-binding protein involved in the post-transcriptional regulation of mRNAs. We report that a large fraction of STAU1 localizes to the mitotic spindle in colorectal cancer HCT116 cells and in non-transformed hTERT-RPE1 cells. Spindle-associated STAU1 partly co-localizes with ribosomes and active sites of translation. We mapped the molecular determinant required for STAU1-spindle association within the first 88 N-terminal amino acids, a domain that is not required for RNA binding. Interestingly, transcriptomic analysis of purified mitotic spindles revealed that 1054 mRNAs and the precursor ribosomal RNA (pre-rRNA), as well as the long non-coding RNAs and small nucleolar RNAs involved in ribonucleoprotein assembly and processing, are enriched on spindles compared with cell extracts. STAU1 knockout causes displacement of the pre-rRNA and of 154 mRNAs coding for proteins involved in actin cytoskeleton organization and cell growth, highlighting a role for STAU1 in mRNA trafficking to spindle. These data demonstrate that STAU1 controls the localization of subpopulations of RNAs during mitosis and suggests a novel role of STAU1 in pre-rRNA maintenance during mitosis, ribogenesis and/or nucleoli reassembly.

Staufen1 is Essential for Cell-Cycle Transitions and Cell Proliferation Via the Control of E2F1 Expression.

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.