TY - JOUR
T1 - XPhosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains
AU - Kwon, Ilmin
AU - Kato, Masato
AU - Xiang, Siheng
AU - Wu, Leeju
AU - Theodoropoulos, Pano
AU - Mirzaei, Hamid
AU - Han, Tina
AU - Xie, Shanhai
AU - Corden, Jeffry L.
AU - McKnight, Steven L.
N1 - Funding Information:
We thank the shared resource cores in Microscopic Imaging, Proteomics and DNA Sequencing at UTSWMC for technical support; Dr. Robert Tycko for provision of the electron micrograph of amyloid fibers included in the graphical abstract; Dr. David Trudgian for help with mass spectrometry; and Drs. Bruce Alberts, Deepak Nijhawan, Michael Brown, and Michael Rosen for helpful comments on the composition of the manuscript. This work was funded by an unrestricted endowment provided S.L.M. by an anonymous donor and NIH grant GM066108 for J.L.C.
PY - 2013/11/21
Y1 - 2013/11/21
N2 - The low-complexity (LC) domains of the products of the fused in sarcoma (FUS), Ewings sarcoma (EWS), and TAF15 genes are translocated onto a variety of different DNA-binding domains and thereby assist in driving the formation of cancerous cells. In the context of the translocated fusion proteins, these LC sequences function as transcriptional activation domains. Here, we show that polymeric fibers formed from these LC domains directly bind the C-terminal domain (CTD) of RNA polymerase II in a manner reversible by phosphorylation of the iterated, heptad repeats of the CTD. Mutational analysis indicates that the degree of binding between the CTD and the LC domain polymers correlates with the strength of transcriptional activation. These studies offer a simple means of conceptualizing how RNA polymerase II is recruited to active genes in its unphosphorylated state and released for elongation following phosphorylation of the CTD. PaperFlick
AB - The low-complexity (LC) domains of the products of the fused in sarcoma (FUS), Ewings sarcoma (EWS), and TAF15 genes are translocated onto a variety of different DNA-binding domains and thereby assist in driving the formation of cancerous cells. In the context of the translocated fusion proteins, these LC sequences function as transcriptional activation domains. Here, we show that polymeric fibers formed from these LC domains directly bind the C-terminal domain (CTD) of RNA polymerase II in a manner reversible by phosphorylation of the iterated, heptad repeats of the CTD. Mutational analysis indicates that the degree of binding between the CTD and the LC domain polymers correlates with the strength of transcriptional activation. These studies offer a simple means of conceptualizing how RNA polymerase II is recruited to active genes in its unphosphorylated state and released for elongation following phosphorylation of the CTD. PaperFlick
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U2 - 10.1016/j.cell.2013.10.033
DO - 10.1016/j.cell.2013.10.033
M3 - Article
C2 - 24267890
AN - SCOPUS:84888440451
VL - 155
SP - 1049
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -