Genomes and Genes
Gene Symbol: POLR2H
Description: RNA polymerase II subunit H
Alias: RPABC3, RPB17, RPB8, DNA-directed RNA polymerases I, II, and III subunit RPABC3, DNA-directed RNA polymerase II subunit H, DNA-directed RNA polymerases I, II, and III 17.1 kDa polypeptide, RPB8 homolog, polymerase (RNA) II (DNA directed) polypeptide H, polymerase (RNA) II subunit H
- 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. ..
- Stevens M, De Clercq E, Balzarini J. The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention. Med Res Rev. 2006;26:595-625 pubmed..As such, targeting of Tat protein (and/or cellular cofactors) provide an interesting perspective for therapeutic intervention in the HIV replicative cycle and may afford lifetime control of the HIV infection. ..
- 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. ..
- 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. ..
- Agostini I, Navarro J, Rey F, Bouhamdan M, Spire B, Vigne R, et al. The human immunodeficiency virus type 1 Vpr transactivator: cooperation with promoter-bound activator domains and binding to TFIIB. J Mol Biol. 1996;261:599-606 pubmed..We demonstrated that the portion of Vpr ranging from amino acids 15 to 77 interacts specifically with the basal transcription factor TFIIB. Also, our data indicated that the N-terminal domain of TFIIB is required for the interaction. ..
- 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. ..
- Garber M, Mayall T, Suess E, Meisenhelder J, Thompson N, Jones K. CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Mol Cell Biol. 2000;20:6958-69 pubmed..Taken together, these results demonstrate that CDK9 phosphorylation is required for high-affinity binding of Tat-P-TEFb to TAR RNA and that the state of P-TEFb phosphorylation may regulate Tat transactivation in vivo. ..
- Kim Y, Bourgeois C, Isel C, Churcher M, Karn J. Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation. Mol Cell Biol. 2002;22:4622-37 pubmed..We conclude that phosphorylation of the RNA polymerase II CTD by CDK9 enhances transcription elongation directly. ..
- Bourgeois C, Kim Y, Churcher M, West M, Karn J. Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Mol Cell Biol. 2002;22:1079-93 pubmed..This novel biochemical function of Spt5 is analogous to the function of NusG, an elongation factor found in Escherichia coli that enhances RNA polymerase stability on templates and shows sequence similarity to Spt5. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Vittal V, Shi L, Wenzel D, Scaglione K, Duncan E, Basrur V, et al. Intrinsic disorder drives N-terminal ubiquitination by Ube2w. Nat Chem Biol. 2015;11:83-9 pubmed publisher..Mechanistic insights reported here provide guiding principles for future efforts to define the N-terminal ubiquitome in cells. ..
- Hirschler Laszkiewicz I, Cavanaugh A, Mirza A, Lun M, Hu Q, Smink T, et al. Rrn3 becomes inactivated in the process of ribosomal DNA transcription. J Biol Chem. 2003;278:18953-9 pubmed..Our results indicate that Rrn3 functions stoichiometrically in rDNA transcription and that its ability to associate with RNA polymerase I is lost upon transcription. ..
- 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. ..
- Freund E, McGuire P. Characterization of RNA polymerase type II from human term placenta. J Cell Physiol. 1986;127:432-8 pubmed..The enzyme was also analyzed by native and denaturing polyacrylamide gel electrophoresis, and evidence is presented that a single polypeptide is radiolabeled with azido purine nucleoside triphosphate photoprobes. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Marcello A, Zoppe M, Giacca M. Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator. IUBMB Life. 2001;51:175-81 pubmed
- ..Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. ..
- McKune K, Moore P, Hull M, Woychik N. Six human RNA polymerase subunits functionally substitute for their yeast counterparts. Mol Cell Biol. 1995;15:6895-900 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Kang X, Hu Y, Li Y, Guo X, Jiang X, Lai L, et al. Structural, biochemical, and dynamic characterizations of the hRPB8 subunit of human RNA polymerases. J Biol Chem. 2006;281:18216-26 pubmedThe RPB8 subunit is present in all three types of eukaryotic RNA polymerases and is highly conserved during evolution...
- Jiang F, Todd N, Li R, Zhang H, Fang H, Stass S. A panel of sputum-based genomic marker for early detection of lung cancer. Cancer Prev Res (Phila). 2010;3:1571-8 pubmed publisher..The gene panel could provide sputum-based markers that have the potential to improve early detection of lung SCCs. ..
- 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. ..
- Bokar J, Shambaugh M, Polayes D, Matera A, Rottman F. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 1997;3:1233-47 pubmed..MT-A70 also contains a long region of homology to the yeast protein SPO8, which is involved in induction of sporulation by an unknown mechanism. ..
- 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. ..
- Jang K, Collins M, Latchman D. The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC. J Acquir Immune Defic Syndr. 1992;5:1142-7 pubmed..The significance of this effect for the life cycle of HIV and its interaction with infected cells is discussed. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- Yuan X, Zhao J, Zentgraf H, Hoffmann Rohrer U, Grummt I. Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO Rep. 2002;3:1082-7 pubmed..The results uncover an interphase for essential protein-protein interactions that facilitate Pol I preinitiation complex formation. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9:554-67 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- De Graeve F, Bahr A, Chatton B, Kedinger C. A murine ATFa-associated factor with transcriptional repressing activity. Oncogene. 2000;19:1807-19 pubmed..Together, these findings suggest that mAM may be involved in the fine-tuning of ATFa-regulated gene expression, by interfering with the assembly or stability of specific preinitiation transcription complexes. ..
- 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. ..
- Birch J, Tan B, Panov K, Panova T, Andersen J, Owen Hughes T, et al. FACT facilitates chromatin transcription by RNA polymerases I and III. EMBO J. 2009;28:854-65 pubmed publisher..Our data also imply that local chromatin dynamics influence transcription of the active rRNA genes by Pol I and of Pol III-transcribed genes. ..
- Wu W, Nishikawa H, Hayami R, Sato K, Honda A, Aratani S, et al. BRCA1 ubiquitinates RPB8 in response to DNA damage. Cancer Res. 2007;67:951-8 pubmed..Here, we report that BRCA1-BARD1 mediates polyubiquitination of RPB8, a common subunit of RNA polymerases, in response to DNA damage...
- 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. ..
- 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. ..
- 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. ..
- 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. ..