Functional association of Gdown1 with RNA polymerase II poised on human genes.

Most human genes are loaded with promoter-proximally paused RNA polymerase II (Pol II) molecules that are poised for release into productive elongation by P-TEFb. We present evidence that Gdown1, the product of the POLR2M gene that renders Pol II responsive to Mediator, is involved in Pol II elongation control. During in vitro transcription, Gdown1 specifically blocked elongation stimulation by TFIIF, inhibited the termination activity of TTF2, and influenced pausing factors NELF and DSIF, but did not affect the function of TFIIS or the mRNA capping enzyme. Without P-TEFb, Gdown1 led to the production of stably paused polymerases in the presence of nuclear extract. Supporting these mechanistic insights, ChIP-Seq demonstrated that Gdown1 mapped over essentially all poised polymerases across the human genome. Our results establish that Gdown1 stabilizes poised polymerases while maintaining their responsiveness to P-TEFb and suggest that Mediator overcomes a Gdown1-mediated block of initiation by allowing TFIIF function.

Falsely Undetectable Prostate-Specific Antigen (PSA) Due to Presence of an Inhibitory Serum Factor: A Case Report and Review of Pertinent Literature.

BACKGROUND Few cases of falsely undetectable PSA due to the presence of an inhibitory serum factor have been reported in the world literature. We present a case of falsely low-to-undetectable PSA with data from a serum dilution series, the current literature on biochemical assay interference, and the implications for prostate cancer salvage treatment. CASE REPORT A 63-year-old man was treated with prostatectomy for high-risk prostate cancer and was found to have a rising PSA after approximately 3 years following surgery. He subsequently transferred his care to a different health system and was found to have an undetectable PSA. He was eventually found to have an elevated PSA once again after the particular assay at this institution was changed. He thus received salvage prostate radiotherapy and androgen deprivation therapy. CONCLUSIONS While falsely low PSA results cannot be explained by the presence of serum heterophile antibodies, competitive antibody interference against the immunoassay reagents or anti-PSA antibodies are possible explanations for the results of the dilution experiments performed in this case study. We suggest that unexpected PSA testing results should raise concern for assay interference and warrant further clinical workup.