title: Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains.
abstract: 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.
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Ilmin
authors.initials: I
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Siheng
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Leeju
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Pano
authors.initials: P
authors.lastname: Theodoropoulos
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mirzaei
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Tina
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Shanhai
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Molecular Biology and Genetics The Johns Hopkins University School of Medicine Baltimore, MD 21205.
authors.forename: Jeffry L
authors.initials: JL
authors.lastname: Corden
authors.affiliation: Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
authors.forename: Steven L
authors.initials: SL
authors.lastname: McKnight
mesh_terms: D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D018895:Microsatellite Repeats; D010766:Phosphorylation; D058105:Polymerization; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D020100:Hydrogels; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D012319:RNA Polymerase II