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Cancer is a multifaceted process and many of its hallmarks involve complex protein-protein interactions that dysregulate gene expression and involves yet-to-be understood activities of RNA helicase A (RHA), also known as DHX9. Human T-cell leukemia virus type 1 (HTLV-1) is a causative of adult T-cell leukemia/lymphoma (ATL), which has no cure. The viral oncoprotein, Tax, is necessary for cell transformation and transactivates gene transcription by associating with promoter DNA, various DNA binding proteins and histone acetyltransferases CBP/p300. Using co-immunoprecipitation assays (coIPs), we observed a physical interaction between CBP, RHA and RNA polymerase II. Likewise, coIPs demonstrated the physical interaction of RHA and HTLV-1’s post-transcriptional control element (PCE), which is necessary for viral RNA translation. Thus we hypothesized that RHA is necessary for the transcriptional, as well as post-transcriptional expression of HTLV-1. RHA (DHX9) gene mutations and amplifications are cataloged in the Cancer Genome Atlas and their significance will be discussed. To test our hypothesis, HTLV-1 LTR-Luc reporter and tax expression plasmids were transfected into HEK293 and HeLa cells and Luc protein and luc RNA were quantified by immunoblot and RT-qPCR, respectively. Exogenous expression of FLAG-RHA (FLAG-RHA) increased HTLV-1 LTR-Luc activity, whereas downregulation of endogenous RHA by siRNA reduced Luc activity to basal levels. Exogenous expression of substitution mutants FLAG-RHA W339A and K417R reduced luc RNA and protein activity. We postulate the W339A mutation abrogated the necessary physical interaction between CBP, RHA and RNA polymerase II. CoIP experiments are needed to document our preliminary data indicating that RHA is necessary for CBP-dependent Tax-mediated HTLV-1 transcription, and its molecular basis is in tethering RNA polymerase II to CBP/p300 and Tax on the HTLV-1 promoter.