PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors

In papillary renal cell carcinomas the TFE3 transcription factor becomes fu sed to the PSF and NonO pre-mRNA splicing factors and most commonly to a pr otein of unknown function designated PRCC, In this: study we have examined the ability of the resulting PRCC-TFE3 and NonO-TFE3 fusions to activate tr anscription from the plasminogen activator inhibitor-1 (PAI-1) promoter. Th e results shea that only fusion to PRCC enhanced transcriptional activation , indicating that the ability to enhance the level of transcription from en dogenous TFE3 promoters is not a consistent feature of TFE3 fusions, In inv estigations of the normal function of PRCC,ve observed that PRCC expressed as a green fluorescent fusion protein colocalizes within the nucleus with S m pre-RNA splicing factors. It was also found that endogenous PRCC is coimm unoprecipitated by antibodies that recognize a variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association with the cellular splic ing machinery is therefore, a common feature of the proteins that become fu sed to TFE3 in papillary renal cell carcinomas.