THEME I: Translation regulation by mRNA-binding proteins

Cold-shock proteins

Cancer cells have major metabolic alterations and have an increased ability to cope with stress. In addition to transcriptional regulation, other translation-modifying mechanisms appear to favor expression of oncogenes and, consequently, growth and resistance of cancer cells. YB-1 is considered as a marker for many cancers and its expression is directly related to cell survival, resistance to chemotherapy and cell proliferation. The potential binding of YB-1 to an inverted CCAT box has been the subject of many studies and has led researchers to consider it as a transcription factor that controls the expression of key genes for cell survival, including MDR1 and Top2α. However, it has recently been found that binding of YB-1 to the CCAT box is probably not taking place. On the other hand, its participation in the regulation of translation is more documented.  YB-1 has a marked cytoplasmic location and strongly binds to cytoplasmic mRNA. Along with PABP-1, it is therefore considered has one of the core-mRNA-binding proteins. Consistently, YB-1 is a translation regulator that may promote the expression of a specific mRNA coding for oncogenes such as EMT factors snail1, VEGF, HIF-1α and Twist.

Schematic view of the selective binding of YB-1 to specific mRNA

Our previous work has shown that overexpressing YB-1 prevents the formation of stress granules in mammalian cells. YB-1 also dissociates mRNA granules preformed in the presence of the TIA-1 in vitro. We were then interested in deciphering the mechanisms which allow YB-1 to form isolated mRNPs.