The Rpb4/7 module connects the Ccr4‐Not complex to elongating RNA polymerase II: implications for the coordination of synthesis and decay (560.10)

It is now known that the synthesis and decay of mRNAs are coordinated; however, the factors involved in this process and the mechanism of how these two distinct events are linked are not known. The Ccr4‐Not complex regulates multiple steps in mRNA metabolism, including RNA polymerase II (RNAPII) elongation and mRNA decay. Like Ccr4‐Not, the Rpb4/7 module of RNAPII has been implicated in both the synthesis and decay of mRNAs and Ccr4‐Not and RPB4 mutants display many similar phenotypes. This suggests that Ccr4‐Not and Rpb4/7 may cooperate to regulate the synthesis and decay of mRNAs. We have shown that Ccr4‐Not directly interacts with RNAPII elongation complexes and stimulates transcription elongation of arrested polymerase in vitro. Here we present new data on the structural requirements for the Ccr4‐Not‐RNAPII interaction and implicate the Rpb4/7 module of RNAPII in the process. Our biochemical data suggests that Rpb4/7 assists in the recruitment of Ccr4‐Not into elongation complexes, which is important for the coordination of transcription elongation and mRNA decay. The coordination of decay and synthesis has been demonstrated during cell stress, and the process is believed to require the remodeling of mRNP complexes and the redistribution of RNA binding factors in the cell. We have mapped the mRNAs bound to Ccr4 and other mRNA decay factors in cells during resting and stressed conditions. The results reveal a dramatic redistribution of decay factors unto mRNAs that correlate with changes in their decay and synthesis. These results provide novel insights into the mechanism of how synthesis and decay pathways are altered during cell stress. Grant Funding Source : NIH GM058672