期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2016
卷号:113
期号:50
页码:E8197-E8206
DOI:10.1073/pnas.1605871113
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:SignificanceRho GTPase and polymerase II (Pol II), two key molecules involved in cellular signaling and transcription in eukaryotic organisms, have been separately studied for more than 2 decades without evidence showing their functional linkage. We provide genetic and biochemical evidence linking these two molecules in an intracellular signaling pathway. Rho GTPases in Arabidopsis and yeast can modulate the phosphorylation status of the Pol II C-terminal domain (CTD) by inhibiting the CTD phosphatases. Our finding renders strong support for a direct or "shortcut" model in transcriptional control. Compared with the classical transcriptional activator/repressor-mediated indirect model, this shortcut model of targeting the core of Pol II likely provides an efficient transcriptional control to rapidly bring about the broad changes in gene expression. Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants expressing a constitutively active form of ROP2 (designated CA1-1), we identified RNA polymerase II (Pol II) C-terminal domain (CTD) phosphatase-like 1 (CPL1) as a transcriptional regulator of ROP2 signaling. We show that ROP2 activation inhibits CPL1 activity by promoting its degradation, leading to an increase in CTD Ser5 and Ser2 phosphorylation. We also observed similar modulation of CTD phosphorylation by yeast Cdc42 GTPase and enhanced degradation of the yeast CTD phosphatase Fcp1 by activated ROP2 signaling. Taken together, our results suggest that modulation of the Pol II CTD code by Rho GTPase signaling represents an evolutionarily conserved mechanism in both unicellular and multicellular eukaryotes.
关键词:Rho GTPase ; ROP GTPase ; Pol II ; CTD code ; CPL1