Figure 6.

Schematic diagram showing a model of how mPinX1t regulates cardiac differentiation. mPinX1 and mPinX1t contain the RNA‐binding domain G‐Patch. This domain allows mPinX1 and mPinX1t to compete with each other for binding to the mRNAs of the cardiac transcription factors Gata4 and Tbx5. Only mPinX1t would interact with Nucleoporin 133 (Nup133), a component of the nuclear pore complex. We speculate that mammalian Nup133 negatively mediates the transport of mRNAs from nucleus to cytoplasm; mPinX1t interacts with Nup133 and relieves its inhibitory effect on the transport of Gata4 and Tbx5 mRNAs from nucleus to cytoplasm. Therefore, in the presence of mPinX1t, more Gata4 and Tbx5 mRNAs can be exported to the cytoplasm for later translation. This would result in larger amount of cardiac transcription factor proteins produced for cardiac differentiation. In the upper part of the figure, what happens in the cytoplasm under different scenarios are indicated. When mPinX1t is overexpressed, mPinX1t protein would bind to the mRNAs of Gata4 and Tbx5; these mPinX1t proteins would also interact with Nup133 to relieve its inhibitor effect on the transport the mRNAs, so more mRNAs are exported to the cytoplasm for translation. The translated Gata4 and Tbx5 proteins would then function as cardiac transcription factors for cardiac differentiation. When mPinX1 is overexpressed, it competes with mPinX1t and binds to Gata4 and Tbx5 mRNAs. Therefore, less mPinX1t protein binds to Gata4 and Tbx5 mRNAs. On the other hand, when mPinX1 is knocked down, mPinX1t is also knocked down; therefore, there is less mPinX1t protein to interact with Nup133. In both cases, mRNA transport inhibitor effect of Nup133 still exists; export of mRNAs of Gata4 and Tbx5 to the cytoplasm would decrease, leading to a decrease in cardiac differentiation.