STAG3 plays a crucial role in the regulation of cytoplasmic condensates, particularly P-bodies and the centrosome, which are essential for post-transcriptional gene expression. Mechanistically, STAG3 is localized predominantly in the cytoplasm, where it interacts with various RNA-binding proteins (RBPs) and components of the RNA-induced silencing complex (RISC). This localization allows STAG3 to influence the stability and localization of mRNAs within these condensates.
In P-bodies, STAG3 is thought to interact with proteins such as DDX6 and TNRC6C, which are known to be involved in mRNA degradation and silencing. By stabilizing these RBPs, STAG3 may facilitate the sequestration of specific mRNAs, thereby repressing their translation. The destabilization of TNRC6C upon STAG3 knockdown indicates that STAG3 is vital for maintaining the integrity of P-bodies, which serve as sites for mRNA storage and degradation.
At the centrosome, STAG3's interaction with microtubule-associated proteins suggests a role in organizing the cytoskeleton, which is critical for the transport of mRNAs to specific cellular locations. The centrosome has been identified as a site for localized translation, and STAG3's presence there may help regulate the translation of mRNAs that are essential for cell fate decisions. The destabilization of centrosome structure upon STAG3 knockdown further supports its role in maintaining the functional integrity of these cytoplasmic condensates, thereby controlling the spatial and temporal aspects of gene expression.