Characterization of RNA helicase A as component of STAT6-dependent enhanceosome.
Signal transducer and activator of transcription 6 (STAT6) is a regulator of transcription for interleukin-4 (IL-4)-induced genes. The ability of STAT6 to activate transcription depends on functional interaction with other transcription factors and coactivators. We have characterized the mechanism of STAT6-mediated transcriptional activation by identifying STAT6 transcription activation domain (TAD) interacting nuclear proteins. The first of the identified proteins was coactivator protein p100, which regulates IL-4-induced transcription by connecting STAT6 with other transcriptional regulators. Here, we describe RNA helicase A (RHA) as a novel component of STAT6 transcriptosome. In vitro and in vivo experiments indicated that RHA did not directly interact with STAT6, but p100 protein was found to mediate the assembly of the ternary complex of STAT6-p100-RHA. In chromatin immunoprecipitation studies RHA together with p100 enhanced the binding of STAT6 on the human Igepsilon promoter after IL-4 stimulation. RHA enhanced the IL-4-induced transcription, and the participation of RHA in IL-4-regulated transcription was supported by RNAi experiments. Our results suggest that RHA has an important role in the assembly of STAT6 transcriptosome. As RHA is also known to interact with chromatin modifying proteins, the RHA containing protein complexes may facilitate the entry of transcriptional apparatus to the IL-4 responsive promoters.
Välineva
Tuuli
T
Institute of Medical Technology, University of Tampere, FI-33014 Tampere, Finland.
Yang
Jie
J
Silvennoinen
Olli
O
D000818:Animals; D001324:Autoantigens / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D053487:DEAD-box RNA Helicases; D006367:HeLa Cells; D006801:Humans; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000378:metabolism / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
D001324:Autoantigens; D007139:Immunoglobulin epsilon-Chains; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D050800:STAT6 Transcription Factor; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases