Genomes and Genes
Gene Symbol: POLR2F
Description: RNA polymerase II subunit F
Alias: HRBP14.4, POLRF, RPABC14.4, RPABC2, RPB14.4, RPB6, RPC15, DNA-directed RNA polymerases I, II, and III subunit RPABC2, DNA-directed RNA polymerase II subunit F, DNA-directed RNA polymerases I, II, and III 14.4 kDa polypeptide, RNA Polymerase II subunit 14.4 kD, RNA polymerases I, II, and III subunit ABC2, polymerase (RNA) II (DNA directed) polypeptide F, polymerase (RNA) II subunit F
- Isel C, Karn J. Direct evidence that HIV-1 Tat stimulates RNA polymerase II carboxyl-terminal domain hyperphosphorylation during transcriptional elongation. J Mol Biol. 1999;290:929-41 pubmed..We conclude that activation of the CDK9 kinase, leading to CTD phosphorylation, occurs only in elongation complexes that have transcribed through the Tat-recognition element, TAR RNA. ..
- He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, et al. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010;38:428-38 pubmed publisher..The ability of Tat to enable two different classes of elongation factors to cooperate and coordinate their actions on the same polymerase enzyme explains why Tat is such a powerful activator of HIV-1 transcription. ..
- Hamasaki T, Okamoto M, Baba M. Identification of novel inhibitors of human immunodeficiency virus type 1 replication by in silico screening targeting cyclin T1/Tat interaction. Antimicrob Agents Chemother. 2013;57:1323-31 pubmed publisher..Thus, a series of compounds described herein are novel inhibitors of HIV-1 transcription through inhibition of CycT1/Tat interaction. ..
- Nekhai S, Jeang K. Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev. Future Microbiol. 2006;1:417-26 pubmed..Rev primarily functions to export unspliced and partially spliced viral RNAs from the nucleus into the cytoplasm. For this activity, Rev cooperates with cellular transport protein CRM1 and RNA helicases DDX1 and DDX3, amongst others. ..
- Ping Y, Rana T. DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation. J Biol Chem. 2001;276:12951-8 pubmed..These findings reveal a molecular mechanism for the negative and positive regulation of transcriptional elongation at the HIV-1 promoter. ..
- Herrmann C, Rice A. Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor. J Virol. 1995;69:1612-20 pubmed..Taken together, these results imply that TAK is a very promising candidate for a cellular factor that mediates Tat transactivation. ..
- Nekhai S, Zhou M, Fernandez A, Lane W, Lamb N, Brady J, et al. HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2, phosphorylates CDK7 and stimulates Tat-mediated transcription. Biochem J. 2002;364:649-57 pubmed..They are also consistent with the observed cell-cycle-specific induction of viral gene transactivation. ..
- Zhao W, Liu Y, Timani K, He J. Tip110 protein binds to unphosphorylated RNA polymerase II and promotes its phosphorylation and HIV-1 long terminal repeat transcription. J Biol Chem. 2014;289:190-202 pubmed publisher..Taken together, these findings have provided additional and mechanistic evidence to support Tip110 function in HIV-1 transcription. ..
- Sawaya B, Khalili K, Gordon J, Taube R, Amini S. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem. 2000;275:35209-14 pubmed..Moreover identification of R73S mutant of Vpr provides a new therapeutic avenue for controlling HIV-1 gene transcription and replication in the infected cells. ..
- Kato H, Sumimoto H, Pognonec P, Chen C, Rosen C, Roeder R. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992;6:655-66 pubmed..We propose the hypothesis that Tat acts as a processivity factor on RNA polymerase II in an analogous manner to TFIIF. ..
- Kiernan R, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, et al. HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J. 1999;18:6106-18 pubmed..These data suggest that acetylation of Tat regulates two discrete and functionally critical steps in transcription, binding to an RNAP II CTD-kinase and release of Tat from TAR RNA. ..
- Southgate C, Zapp M, Green M. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature. 1990;345:640-2 pubmed..Our results further suggest that cellular proteins that bind specifically to TAR RNA or TAR DNA may not be essential for Tat-responsiveness. ..
- Deng L, Ammosova T, Pumfery A, Kashanchi F, Nekhai S. HIV-1 Tat interaction with RNA polymerase II C-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter. J Biol Chem. 2002;277:33922-9 pubmed..We suggest that CDK2 is part of a transcription complex that is required for Tat-dependent transcription and that interaction of Tat with CTD and a dynamic association of Tat with CDK2/cyclin E stimulated CTD phosphorylation by CDK2. ..
- del Río Portilla F -, Gaskell A, Gilbert D, Ladias J, Wagner G. Solution structure of the hRPABC14.4 subunit of human RNA polymerases. Nat Struct Biol. 1999;6:1039-42 pubmed..4 structure accounts for mutagenesis results in Saccharomyces cerevisiae and provides a structural working model for elucidating the role of this subunit in the molecular architecture and function of the human nuclear RNA polymerases. ..
- Garrido Godino A, GarcÃa LÃ³pez M, GarcÃa MartÃnez J, Pelechano V, Medina D, PÃ©rez OrtÃn J, et al. Rpb1 foot mutations demonstrate a major role of Rpb4 in mRNA stability during stress situations in yeast. Biochim Biophys Acta. 2016;1859:731-43 pubmed publisher..foot region of RNA polymerase II affect the assembly of the complex by altering the correct association of both the Rpb6 and the Rpb4/7 dimer...
- HU W, Hughes S. HIV-1 reverse transcription. Cold Spring Harb Perspect Med. 2012;2: pubmed publisher..In keeping with the theme of the collection, the emphasis is on HIV-1 and HIV-1 RT. ..
- Okamoto H, Sheline C, Corden J, Jones K, Peterlin B. Trans-activation by human immunodeficiency virus Tat protein requires the C-terminal domain of RNA polymerase II. Proc Natl Acad Sci U S A. 1996;93:11575-9 pubmed..These results suggest that effects of Tat on the processivity of RNA polymerase II require proteins that are associated with the CTD and may result in the phosphorylation of the CTD. ..
- Yankulov K, Bentley D. Transcriptional control: Tat cofactors and transcriptional elongation. Curr Biol. 1998;8:R447-9 pubmed..Recent results show that two cellular cyclin-dependent kinases, which phosphorylate the carboxy-terminal domain of the RNA polymerase II large subunit, contact Tat and contribute to the control of transcriptional elongation. ..
- Wu Baer F, Sigman D, Gaynor R. Specific binding of RNA polymerase II to the human immunodeficiency virus trans-activating region RNA is regulated by cellular cofactors and Tat. Proc Natl Acad Sci U S A. 1995;92:7153-7 pubmed..These results suggest that Tat may function to alter RNA polymerase II, which is paused due to its binding to HIV-1 TAR RNA with resultant stimulation of its transcriptional elongation properties. ..
- ..Now, Pagans and colleagues report that the lysine methyltransferase Set7/9-KMT7 associates with Tat to stimulate RNA polymerase II elongation of the integrated provirus. Set7/9-KMT7 also methylates Tat, and this enhances Tat function. ..
- Acker J, Wintzerith M, Vigneron M, Kedinger C. A 14.4 KDa acidic subunit of human RNA polymerase II with a putative leucine-zipper. DNA Seq. 1994;4:329-31 pubmed..and compared to that of the homologous subunit of Saccharomyces cerevisiae polymerase (ABC23, encoded by the RPB6/RPO26 gene)...
- Kayukawa K, Makino Y, Yogosawa S, Tamura T. A serine residue in the N-terminal acidic region of rat RPB6, one of the common subunits of RNA polymerases, is exclusively phosphorylated by casein kinase II in vitro. Gene. 1999;234:139-47 pubmedb>RPB6 is one of the common subunits of all eukaryotic RNA polymerases and is indispensable for the enzyme function. Here, we isolated a rat cDNA encoding RPB6. It contained 127 amino acid (a.a.) residues...
- Okamoto T. [Positive and negative regulation of transcription from HIV provirus]. Uirusu. 2011;61:81-9 pubmed..HIV is unique in that it contains virus-specific transcriptional activator called Tat. ..
- Xiao H, Palhan V, Yang Y, Roeder R. TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes. EMBO J. 2000;19:956-63 pubmed..These data demonstrate a molecular mechanism for TIP30/CC3 function and suggest a novel pathway for regulating apoptosis. ..
- Nekhai S, Shukla R, Kumar A. A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity. J Virol. 1997;71:7436-41 pubmed..Importantly, the Tat-associated kinase markedly induced CAK. We suggest that the mechanism of Tat-mediated processive transcription of the HIV-1 promoter includes a Tat-associated CAK activator. ..
- Cujec T, Okamoto H, Fujinaga K, Meyer J, Chamberlin H, Morgan D, et al. The HIV transactivator TAT binds to the CDK-activating kinase and activates the phosphorylation of the carboxy-terminal domain of RNA polymerase II. Genes Dev. 1997;11:2645-57 pubmed..Our data identify a cellular protein that interacts with the activation domain of Tat, demonstrate that this interaction is critical for the function of Tat, and provide a mechanism by which Tat increases the processivity of Pol II. ..
- Ramanathan Y, Reza S, Young T, Mathews M, PE ERY T. Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate. J Virol. 1999;73:5448-58 pubmed..We suggest a model in which Tat first interacts with P-TEFb to form the TAK complex that engages with TAR RNA and the elongating transcription complex, resulting in hyperphosphorylation of the CTD on serine 5 residues. ..
- Antonacopoulou A, Grivas P, Skarlas L, Kalofonos M, Scopa C, Kalofonos H. POLR2F, ATP6V0A1 and PRNP expression in colorectal cancer: new molecules with prognostic significance?. Anticancer Res. 2008;28:1221-7 pubmedDNA-directed RNA polymerase II subunit F (POLR2F), a subunit of the V0 domain of the vacuolar ATPase (ATP6V0A1) and the prion protein (PRNP) are molecules of potential importance in carcinogenesis and targeted cancer therapy...
- Acker J, de Graaff M, Cheynel I, Khazak V, Kedinger C, Vigneron M. Interactions between the human RNA polymerase II subunits. J Biol Chem. 1997;272:16815-21 pubmed..These subunits, which are able to homodimerize and to interact, may constitute the nucleation center for polymerase assembly, by providing a large interface to most of the other subunits. ..
- Zhou M, Kashanchi F, Jiang H, Ge H, Brady J. Phosphorylation of the RAP74 subunit of TFIIF correlates with Tat-activated transcription of the HIV-1 long terminal repeat. Virology. 2000;268:452-60 pubmed..Of importance, the exogenous RAP74 was rapidly phosphorylated in the presence of Tat. These results suggest that RAP74 phosphorylation is one important step, of several, in the Tat transactivation cascade. ..
- Parada C, Roeder R. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999;18:3688-701 pubmed..Our results indicate that Tat-SF is a Tat cofactor-containing RNA Pol II complex whose recruitment to the promoter provides elongation factors important for Tat-enhanced HIV-1 transcription following TAR RNA synthesis. ..
- Kino T, Gragerov A, Kopp J, Stauber R, Pavlakis G, Chrousos G. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med. 1999;189:51-62 pubmed..The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS. ..
- Cramer P, Bushnell D, Fu J, Gnatt A, Maier Davis B, Thompson N, et al. Architecture of RNA polymerase II and implications for the transcription mechanism. Science. 2000;288:640-9 pubmed..A clamp on the DNA nearer the active center, formed by Rpb1, Rpb2, and Rpb6, may be locked in the closed position by RNA, accounting for the great stability of transcribing complexes...
- Yang X, Herrmann C, Rice A. The human immunodeficiency virus Tat proteins specifically associate with TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II for function. J Virol. 1996;70:4576-84 pubmed..These observations strengthen the proposal that the mechanism of action of Tat involves the recruitment or activation of TAK, resulting in activated transcription through phosphorylation of the CTD. ..
- García Martínez L, Mavankal G, Neveu J, Lane W, Ivanov D, Gaynor R. Purification of a Tat-associated kinase reveals a TFIIH complex that modulates HIV-1 transcription. EMBO J. 1997;16:2836-50 pubmed..These results define a cellular kinase complex whose activity is modulated by Tat to result in activation of HIV-1 trancription. ..
- Nogues G, Kadener S, Cramer P, Bentley D, Kornblihtt A. Transcriptional activators differ in their abilities to control alternative splicing. J Biol Chem. 2002;277:43110-4 pubmed..Rapid, highly processive transcription favors EDI exon skipping, whereas slower, less processive transcription favors inclusion. ..
- Agbottah E, Zhang N, Dadgar S, Pumfery A, Wade J, Zeng C, et al. Inhibition of HIV-1 virus replication using small soluble Tat peptides. Virology. 2006;345:373-89 pubmed..Finally, we show that these peptides do not allow loading of the catalytic domain of the cdk/cyclin complex onto the HIV-1 promoter in vivo. ..
- Chun R, Jeang K. Requirements for RNA polymerase II carboxyl-terminal domain for activated transcription of human retroviruses human T-cell lymphotropic virus I and HIV-1. J Biol Chem. 1996;271:27888-94 pubmed..Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD. ..
- Wani S, Hirose Y, Ohkuma Y. Human RNA polymerase II-associated protein 2 (RPAP2) interacts directly with the RNA polymerase II subunit Rpb6 and participates in pre-mRNA 3'-end formation. Drug Discov Ther. 2014;8:255-61 pubmed publisher..Here, we demonstrate that the C-terminal region of RPAP2 interacts directly with the Pol II subunit Rpb6. Chromatin immunoprecipitation analyses of the MYC and GAPDH protein-coding genes revealed that RPAP2 occupied the ..
- Jones E, Kimura H, Vigneron M, Wang Z, Roeder R, Cook P. Isolation and characterization of monoclonal antibodies directed against subunits of human RNA polymerases I, II, and III. Exp Cell Res. 2000;254:163-72 pubmed..We now describe eight different monoclonal antibodies that react specifically with RPB6 (also known as RPA20, RPB14...
- Agostini I, Navarro J, Bouhamdan M, Willetts K, Rey F, Spire B, et al. The HIV-1 Vpr co-activator induces a conformational change in TFIIB. FEBS Lett. 1999;450:235-9 pubmed..Our data show a correlation between the ability of Vpr-mutated proteins to stimulate transcription and their ability to induce a conformational change in TFIIB, indicating a functional relevance of the Vpr-TFIIB interaction. ..
- Wilusz J. Putting an 'End' to HIV mRNAs: capping and polyadenylation as potential therapeutic targets. AIDS Res Ther. 2013;10:31 pubmed publisher..This review describes these post-transcriptional novelties of HIV gene expression as well as their implications in viral biology and as possible targets for therapeutic intervention. ..
- Ivanov D, Kwak Y, Nee E, Guo J, García Martínez L, Gaynor R. Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation. J Mol Biol. 1999;288:41-56 pubmed..These results demonstrate that cyclin T1 interactions with Tat and TAR RNA are critical for activation of HIV-1 gene expression. ..
- Kaehlcke K, Dorr A, Hetzer Egger C, Kiermer V, Henklein P, Schnoelzer M, et al. Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation. Mol Cell. 2003;12:167-76 pubmed..We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II. ..
- Schlegel B, Green V, Ladias J, Parvin J. BRCA1 interaction with RNA polymerase II reveals a role for hRPB2 and hRPB10alpha in activated transcription. Proc Natl Acad Sci U S A. 2000;97:3148-53 pubmed..No other Pol II subunits tested inhibited activated transcription in these assays. Furthermore, hRPB10alpha, but not hRPB2, blocked Sp1-dependent activation. ..
- Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9:554-67 pubmed
- Zhou M, Halanski M, Radonovich M, Kashanchi F, Peng J, Price D, et al. Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Mol Cell Biol. 2000;20:5077-86 pubmed..These studies suggest that the ability of Tat to increase transcriptional elongation may be due to its ability to modify the substrate specificity of the CDK9 complex. ..
- Kershnar E, Wu S, Chiang C. Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes. J Biol Chem. 1998;273:34444-53 pubmed
- Pusch C, Wang Z, Roe B, Blin N. Genomic structure of the RNA polymerase II small subunit (hRPB14.4) locus (POLRF) and mapping to 22q13.1 by sequence identity. Genomics. 1996;34:440-2 pubmed
- Romano G, Kasten M, De Falco G, Micheli P, Khalili K, Giordano A. Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression. J Cell Biochem. 1999;75:357-68 pubmed
- Hu P, Wu S, Sun Y, Yuan C, Kobayashi R, Myers M, et al. Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits. Mol Cell Biol. 2002;22:8044-55 pubmed..Our results provide a characterization of human RNA polymerase III and show that the RPC5 subunit is essential for transcription. ..
- Liu Y, Suñé C, Garcia Blanco M. Human immunodeficiency virus type 1 Tat-dependent activation of an arrested RNA polymerase II elongation complex. Virology. 1999;255:337-46 pubmed..These data indicate that Tat can activate elongation of RNA polymerase by modifying an already elongating transcription complex. The data also suggest the possibility that Tat can interact with initiation complexes. ..
- Zhou C, Rana T. A bimolecular mechanism of HIV-1 Tat protein interaction with RNA polymerase II transcription elongation complexes. J Mol Biol. 2002;320:925-42 pubmed..These findings suggest that two Tat molecules are involved in performing various functions during a single round of HIV-1 mRNA synthesis. ..
- Suñé C, Hayashi T, Liu Y, Lane W, Young R, Garcia Blanco M. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription. Mol Cell Biol. 1997;17:6029-39 pubmed..Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150. ..
- Suñé C, Garcia Blanco M. Transcriptional cofactor CA150 regulates RNA polymerase II elongation in a TATA-box-dependent manner. Mol Cell Biol. 1999;19:4719-28 pubmed..In addition, we also provide evidence suggesting a role for CA150 in the regulation of cellular transcriptional processes. ..
- Jeang K. Tat, Tat-associated kinase, and transcription. J Biomed Sci. 1998;5:24-7 pubmed..Here we review, in brief, the role of Tat-associated kinase in Tat-activated transcription. We discuss evidence that suggests involvement of TFIIH and/or P-TEFb. ..
- Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L. Will diverse Tat interactions lead to novel antiretroviral drug targets?. Curr Drug Targets. 2006;7:1595-606 pubmed..Nevertheless, Tat remains an attractive, virus-specific molecule and detailed understanding of specific protein interaction holds promise for future drug discovery. ..
- Kino T, Tsukamoto M, Chrousos G. Transcription factor TFIIH components enhance the GR coactivator activity but not the cell cycle-arresting activity of the human immunodeficiency virus type-1 protein Vpr. Biochem Biophys Res Commun. 2002;298:17-23 pubmed..These findings suggest that TFIIH participates in Vpr's GR coactivating activity, at a step beyond its interaction with p300/CBP. ..
- Zhang H, Sun L, Liang J, Yu W, Zhang Y, Wang Y, et al. The catalytic subunit of the proteasome is engaged in the entire process of estrogen receptor-regulated transcription. EMBO J. 2006;25:4223-33 pubmed..These results revealed a mechanism by which the proteasome machinery is recruited in ER-mediated gene transcription. Our experiments also provided evidence implicating SRC coactivators in gene transcription elongation. ..
- Nilson K, Price D. The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency. Genet Res Int. 2011;2011:726901 pubmed publisher..HIV, the causative agent of AIDS, is a worldwide health concern. It is hoped that knowledge of the mechanisms regulating the expression of the HIV genome will lead to treatments and ultimately a cure. ..
- Poon B, Chen I. Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA. J Virol. 2003;77:3962-72 pubmed..These results attribute a new function to HIV-1 Vpr and implicate Vpr as a critical component in expression from unintegrated HIV-1 DNA...