The Staufen1-dependent cell cycle regulon or how a misregulated RNA-binding protein leads to cancer.

Abstract

In recent years, an increasing number of reports have linked the RNA-binding protein Staufen1 (STAU1) to the control of cell decision making. In non-transformed cells, STAU1 balances the expression of messenger RNA (mRNA) regulons that regulate differentiation and well-ordered cell division. Misregulation of STAU1 expression and/or functions changes the fragile balance in the expression of pro- and anti-proliferative and apoptotic genes and favours a novel equilibrium that supports cell proliferation and cancer development. The misregulation of STAU1 functions causes multiple coordinated modest effects in the post-transcriptional regulation of many RNA targets that code for cell cycle regulators, leading to dramatic consequences at the cellular level. The new tumorigenic equilibrium in STAU1-mediated gene regulation observed in cancer cells can be further altered by a slight increase in STAU1 expression that favours expression of pro-apoptotic genes and cell death. The STAU1-dependent cell cycle regulon is a good model to study how abnormal expression of an RNA-binding protein promotes cell growth and provides an advantageous selection of malignant cells in the first step of cancer development.