THOC5, a member of mRNA export complex, as a key mRNP biogenesis factor in cell differentiationGCOE Program Seminar(Global Education Seminar)

THOC5/Fms interacting protein (FMIP), a member of the mRNA export complex. (THO), was originally identified as a substrate for the Macrophage Colony Stimulating Factor (M-CSF) receptor tyrosine kinase, Fms. THOC5 is phosphorylated not only by several tyrosine kinases, but also by protein kinase C, by the downstream kinase from insulin stimulus or ATM kinase, suggesting that extracellular stimulation regulates the function of THOC5. Using interferon inducible THOC5 knockout mice, we have shown that THOC5 is essential at an early stage of mouse development and that this gene is essential for survival in adult mice. In these knockout mice, bone marrow cells become apoptotic, hematopoietic progenitor cell numbers collapse and the animals become anemic. Surprisingly, only 2.9% of the total genes are affected by the depletion of THOC5 in fibroblasts under normal condition, however under stress conditions or upon stimulation with growth factors, a number of THOC5 dependent genes increased. We further identified mRNAs which were detected in the nucleus as spliced forms, but not exported into the cytoplasm in the absence of THOC5. A half of genes were involved in differentiation processes, suggesting that THOC5 may play a role in fine tuning differentiation processes dependent upon the extracellular conditions.