核醣核酸聚合酶第四次單元RPB4在轉錄及訊息核醣核酸降解過程之功能分析

Abstract

Gene expression involves several distinct stages, which are tightly controlled and coordinated. Although the detailed mechanism of each stage is well established, we are still lacking the linkage of how different processes are connected. In Saccharomyces cerevisiae, Rpb4p, which was discovered as a RNA polymerase subunit, is reported to involve in mRNA processing, mRNA export, translation and mRNA degradation, suggesting a role of coordinator. In this study, we aimed to explore the functional characters of RPB4 in both transcription and mRNA degradation in mammalian system. We found that RPB4 located at P-bodies, which accommodate translationally repressed mRNPs and proteins involved in mRNA degradation. In addition, RPB4 interacted with DCP1a, DCP2, DDX6, EDC3 and CAF1a in RNA-independent manner. By tethering RPB4 to luciferase reporter mRNA, we further provided evidences that RPB4 is functionally related to mRNA decay machinery. Interestingly, we observed that RPB4 can translocate from cytoplasm to nucleus and associate with phosporylated RNA polymerase II in response to heat shock stress. Knockdown of RPB4 resulted in down-regulation of proteins involved in mRNA metabolism. Taken together, these findings imply that RPB4 might modulate specific class mRNAs’ turnover by coordinating their metabolic processes.