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Gene Review

POLR2A  -  polymerase (RNA) II (DNA directed)...

Homo sapiens

Synonyms: DNA-directed RNA polymerase II subunit A, DNA-directed RNA polymerase II subunit RPB1, DNA-directed RNA polymerase III largest subunit, POLR2, POLRA, ...
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Disease relevance of POLR2A

  • To this end, we applied a glutathione S-transferase-pulldown assay to extracts from Sf9 insect cells, which were coinfected with all possible combinations of recombinant baculoviruses expressing hRPB subunits, either as untagged polypeptides or as glutathione S-transferase fusion proteins [1].

High impact information on POLR2A

  • Although they are absolutely required for viability in these organisms, C-terminal tandem repeats do not occur in RPB1 sequences from diverse eukaryotic taxa [2].
  • In recent years a great deal of biochemical and genetic research has focused on the C-terminal domain (CTD) of the largest subunit (RPB1) of DNA-dependent RNA polymerase II [2].
  • Sequences within RPB1 encompass several of the conserved catalytic domains that are common to eubacterial, archaeal, and eukaryotic nuclear-encoded RNA polymerases [3].
  • In addition, the presence of introns and a heptapeptide C-terminal repeat in the Mastigamoeba RPB1 sequence, features that are typically associated with more recently derived eukaryotic groups, raise provocative questions regarding models of protist evolution that depend almost exclusively on rDNA sequence analyses [3].
  • Mutations in RPB1 and RPB2, the genes encoding the two largest subunits of RNAP II, were identified as suppressors of ssu72-2 [4].

Biological context of POLR2A

  • As an initial approach to characterizing the molecular structure of the human RNA polymerase II (hRPB), we systematically investigated the protein-protein contacts that the subunits of this enzyme may establish with each other [1].
  • The RpIILS gene consists of 29 exons [5].
  • The sequence of the 5' flanking region is highly conserved as compared with that of the mouse RpIILS and contains several SP1-binding sites, a CCAAT sequence and a sequence homologous to a heat-shock element [5].
  • Surprisingly, we found that approximately 30% of genes in the 30-Mb region possessed an E2F1 binding site in a core promoter and E2F1 was bound near to 83% of POLR2A-bound sites [6].
  • Two major phosphorylation sites have been identified in the Rpb1 carboxyl terminal domain, serine 2 (Ser-2) or serine 5 (Ser-5) of the YSPTSPS heptapeptide repeat [7].

Anatomical context of POLR2A

  • Epitope-tagged recombinant human RPB1 subunits were expressed in mouse fibroblasts [8].
  • We demonstrate that incorporation of LNA into 10-23 motif DNAzymes increases their efficacy in mRNA degradation and that, in a cell-free system, the 10-23 motif LNAzyme can adequately discriminate and recognize an SNP in the large subunit of RNA polymerase II (POLR2A), an essential gene frequently involved in LOH in cancer cells [9].
  • We now characterize a different cell line that has a temperature-sensitive defect in cell cycle progression, and find that it also has a mutation in RPB1 [10].
  • To gain a better understanding of RNAP II evolution, and the presumed artifact relating to green plants and red algae, we isolated and analyzed RPB1 from representatives of Glaucocystophyta, the third eukaryotic group with primary plastids [11].

Associations of POLR2A with chemical compounds

  • Alpha-Amanitin-promoted degradation of RPB1 was prevented in cells exposed to actinomycin D, another transcriptional inhibitor [8].
  • POLR2A was selected since it reduced variability between samples, demonstrated levels of expression similar to those of the genes of interest, and its expression was not modified by capecitabine treatment in samples from preclinical studies [12].
  • Treatment of yeast and human cells with DNA-damaging agents elicits lysine 48-linked polyubiquitylation of Rpb1, the largest subunit of RNA polymerase II (Pol II), which targets Pol II for proteasomal degradation [13].
  • In this paper, we show that hydrogen peroxide (H(2)O(2)) causes significant ubiquitination and proteasomal degradation of Rpb1 by mechanisms that are distinct from those employed after UV irradiation [14].
  • To further test this hypothesis, we sequenced a fragment of the largest subunit of the RNA polymerase II (RPB1) from five foraminiferans, two cercozoans and the testate filosean Gromia oviformis [15].

Enzymatic interactions of POLR2A

  • The efficiency to promote the dephosphorylation of both proteins matches their capacity to inhibit purified Cdk9 kinase, suggesting that Cdk9 is the major kinase phosphorylating hSpt5 and Rpb1 in vivo [16].

Other interactions of POLR2A

  • We now report the results obtained for the last subunit (hRPB4; Mol. Cell. Biol. 18 (1998) 1935-1945) and propose an essentially complete picture of the potential interactions occurring within hRPB [17].
  • Cdk9 dependent phosphorylation of Rpb1 and hSpt5 followed by Pin1 interaction might thus contribute to the regulation of transcription, pre-mRNA maturation, and the dynamics of these proteins in interphase and mitosis [16].
  • When bound to RNAP II, Mg(B) is coordinated by the beta and gamma phosphates of the NTP, Rpb1 residues D481 and D483 and Rpb2 residue D837 [18].
  • These structural effects of Zn2 binding on TFIIB may have a critical role in interactions with its binding partners, such as the Rpb1 subunit of RNA polymerase II [19].
  • We have found that in murine fibroblasts exposure to alpha-amanitin triggered degradation of the RPB1 subunit, while other RNAPII subunits, RPB5 and RPB8, remained almost unaffected [8].

Analytical, diagnostic and therapeutic context of POLR2A

  • Two other charged replacements, G363E and G363K, were constructed by site-directed mutagenesis and suppress both TFIIB E62K and Rpb1 N445S, whereas neither G363A nor G363P exhibited any effect [20].


  1. Interactions between the human RNA polymerase II subunits. Acker, J., de Graaff, M., Cheynel, I., Khazak, V., Kedinger, C., Vigneron, M. J. Biol. Chem. (1997) [Pubmed]
  2. Evolution of the RNA polymerase II C-terminal domain. Stiller, J.W., Hall, B.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Amitochondriate amoebae and the evolution of DNA-dependent RNA polymerase II. Stiller, J.W., Duffield, E.C., Hall, B.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Role for the Ssu72 C-terminal domain phosphatase in RNA polymerase II transcription elongation. Reyes-Reyes, M., Hampsey, M. Mol. Cell. Biol. (2007) [Pubmed]
  5. The human gene encoding the largest subunit of RNA polymerase II. Mita, K., Tsuji, H., Morimyo, M., Takahashi, E., Nenoi, M., Ichimura, S., Yamauchi, M., Hongo, E., Hayashi, A. Gene (1995) [Pubmed]
  6. Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome. Bieda, M., Xu, X., Singer, M.A., Green, R., Farnham, P.J. Genome Res. (2006) [Pubmed]
  7. BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II. Starita, L.M., Horwitz, A.A., Keogh, M.C., Ishioka, C., Parvin, J.D., Chiba, N. J. Biol. Chem. (2005) [Pubmed]
  8. In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. Nguyen, V.T., Giannoni, F., Dubois, M.F., Seo, S.J., Vigneron, M., Kédinger, C., Bensaude, O. Nucleic Acids Res. (1996) [Pubmed]
  9. Evaluation of LNA-modified DNAzymes targeting a single nucleotide polymorphism in the large subunit of RNA polymerase II. Fluiter, K., Frieden, M., Vreijling, J., Koch, T., Baas, F. Oligonucleotides. (2005) [Pubmed]
  10. A mutation in the largest (catalytic) subunit of RNA polymerase II and its relation to the arrest of the cell cycle in G(1) phase. Sugaya, K., Sasanuma, S., Cook, P.R., Mita, K. Gene (2001) [Pubmed]
  11. The largest subunit of RNA polymerase II from the Glaucocystophyta: functional constraint and short-branch exclusion in deep eukaryotic phylogeny. Stiller, J.W., Harrell, L. BMC Evol. Biol. (2005) [Pubmed]
  12. Validation of real-time reverse-transcription-polymerase chain reaction for quantification of capecitabine-metabolizing enzymes. Macpherson, J.S., Jodrell, D.I., Guichard, S.M. Anal. Biochem. (2006) [Pubmed]
  13. ELA1 and CUL3 Are Required Along with ELC1 for RNA Polymerase II Polyubiquitylation and Degradation in DNA-Damaged Yeast Cells. Ribar, B., Prakash, L., Prakash, S. Mol. Cell. Biol. (2007) [Pubmed]
  14. A novel hydrogen peroxide-induced phosphorylation and ubiquitination pathway leading to RNA polymerase II proteolysis. Inukai, N., Yamaguchi, Y., Kuraoka, I., Yamada, T., Kamijo, S., Kato, J., Tanaka, K., Handa, H. J. Biol. Chem. (2004) [Pubmed]
  15. Foraminifera and Cercozoa share a common origin according to RNA polymerase II phylogenies. Longet, D., Archibald, J.M., Keeling, P.J., Pawlowski, J. Int. J. Syst. Evol. Microbiol. (2003) [Pubmed]
  16. The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9. Lavoie, S.B., Albert, A.L., Handa, H., Vincent, M., Bensaude, O. J. Mol. Biol. (2001) [Pubmed]
  17. Interactions between the full complement of human RNA polymerase II subunits. Schaller, S., Grandemange, S., Shpakovski, G.V., Golemis, E.A., Kedinger, C., Vigneron, M. FEBS Lett. (1999) [Pubmed]
  18. The highly conserved glutamic acid 791 of Rpb2 is involved in the binding of NTP and Mg(B) in the active center of human RNA polymerase II. Langelier, M.F., Baali, D., Trinh, V., Greenblatt, J., Archambault, J., Coulombe, B. Nucleic Acids Res. (2005) [Pubmed]
  19. Probing Zn2+-binding effects on the zinc-ribbon domain of human general transcription factor TFIIB. Ghosh, M., Elsby, L.M., Mal, T.K., Gooding, J.M., Roberts, S.G., Ikura, M. Biochem. J. (2004) [Pubmed]
  20. Evidence that the Tfg1/Tfg2 dimer interface of TFIIF lies near the active center of the RNA polymerase II initiation complex. Freire-Picos, M.A., Krishnamurthy, S., Sun, Z.W., Hampsey, M. Nucleic Acids Res. (2005) [Pubmed]
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