Phosphorylation-dependent THRAP3 RNA-binding in prostate cancer

Here, we focus on Thyroid Hormone Receptor-Associated Protein 3 (THRAP3), an RNA-binding protein implicated in mRNA splicing, stability, and DNA damage response that our prior studies identified as a CIT substrate. THRAP3 silencing and overexpression diminished and increased, respectively, CaP cell proliferation, mimicking CIT’s effects. By performing CLIP-Seq assay, we identified several hundreds of CIT-dependent THRAP3-bound transcripts, which were also enriched for functions in cell proliferation.

Overexpression of CIT-induced THRAP3-bound transcripts promoted growth of CaP cell lines, organoids and xenografts. These findings define a novel mechanism by which CIT rewires alternative splicing in CaP and present new therapeutic opportunities for targeting aggressive CaP.