Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains

Cell. 2013 Nov 21;155(5):1049-1060. doi: 10.1016/j.cell.2013.10.033.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • HeLa Cells
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / metabolism
  • Microsatellite Repeats
  • Phosphorylation
  • Polymerization
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism*
  • RNA-Binding Protein EWS / metabolism
  • RNA-Binding Protein FUS / chemistry
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism
  • TATA-Binding Protein Associated Factors / chemistry
  • TATA-Binding Protein Associated Factors / metabolism
  • Transcriptional Activation*

Substances

  • Hydrogels
  • RNA-Binding Protein EWS
  • RNA-Binding Protein FUS
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors
  • RNA Polymerase II