RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor

Kostya I. Panov, Tatiana B. Panova, Olivier Gadal, Kaori Nishiyama, Takashi Saito, Jackie Russell, Joost C. B. M. Zomerdijk

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    34 Citations (Scopus)


    Eukaryotic RNA polymerases are large complexes, 12 subunits of which are structurally or functionally homologous across the three polymerase classes. Each class has a set of specific subunits, likely targets of their cognate transcription factors. We have identified and characterized a human RNA polymerase I (Poll I)-specific subunit, previously identified as ASE-1 (antisense of ERCC1) and as CD3 epsilon-associated signal transducer (CAST), and here termed CAST or human Pol I-associated factor of 49 kDa (hPAF49), after mouse orthologue PAF49. We provide evidence for growth-regulated Tyr phosphorylation of CAST/hPAF49, specifically in initiation-competent Pol I[3 complexes in HeLa cells, at a conserved residue also known to be important for signaling during T-cell activation. CAST/hPAF49 can interact with activator upstream binding factor (UBF) and, weakly, with selectivity factor 1 (SL1) at the rDNA (ribosomal DNA repeat sequence encoding the 18S, 5.8S, and 28S rRNA genes) promoter. CAST/hPAF49-specific antibodies and excess CAST/hPAF49 protein, which have no effect on basal Pol I transcription, inhibit UBF-activated transcription following functional SLl-Pol I-rDNA complex assembly and disrupt the interaction of UBF with CAST/hPAF49, suggesting that interaction of this Pol I-specific subunit with UBF is crucial for activation. Drawing on parallels between mammalian and Saccharomyces cerevisiae Pol I transcription machineries, we advance one model for CAST/hPAF49 function in which the network of interactions of Pol I-specific subunits with UBF facilitates conformational changes of the polymerase, leading to stabilization of the Poll I-template complex and, thereby, activation of transcription.

    Original languageEnglish
    Pages (from-to)5436-5448
    Number of pages13
    JournalMolecular and Cellular Biology
    Issue number14
    Publication statusPublished - Jul 2006


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