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 Stau155-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.
Highlights
It is well accepted that post-transcriptional mechanisms of gene regulation are active to properly link protein synthesis to cell needs [1,2]
Analysis of Stau1 levels revealed a high and stable expression during the S and G2 phases followed by a striking decrease ∼9 h post-double thymidine block (DTB) release, a decrease that parallels those of the mitotic markers cyclin B1 and Aurora A (Supplementary Figure S1)
The periodic expression of cell cycle regulatory proteins is a consequence of their controlled synthesis coupled to their targeted proteolysis
Summary
It is well accepted that post-transcriptional mechanisms of gene regulation are active to properly link protein synthesis to cell needs [1,2]. Stau is involved in several posttranscriptional mechanisms that control gene expression including mRNA transport [4,5,9], translation [3,10,11], decay [6,12], nuclear export [13,14] and splicing [14]. All these functions are likely very important for cell physiology as compelling data indicate that Stau is involved in cell differentiation [12,15,16,17,18,19,20], dendritic spine morphogenesis [9,21] and long-term synaptic plasticity [21], a cellular mechanism for long term memory. Stau is a multifunctional protein and many of its functions are related to post-transcriptional regulation of gene expression
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