Affinage

POLR2D

DNA-directed RNA polymerase II subunit RPB4 · UniProt O15514

Round 2 corrected
Length
142 aa
Mass
16.3 kDa
Annotated
2026-04-28
82 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR2D (RPB4) is a core subunit of RNA polymerase II that forms a dissociable heterodimer with RPB7 (POLR2G) and is essential for normal Pol II transcriptional activity, stress-responsive transcription, and the coordination of mRNA synthesis with downstream mRNA fate. The RPB4/RPB7 heterodimer docks onto the Pol II core through contacts between the RPB4 N-terminus and RPB2 and between the RPB7 RNP domain and the Rpb1 linker, stabilizing pre-initiation complexes and mediating a post-recruitment step in transcription initiation that requires the OB-fold RNA-binding surface of RPB7 (PMID:9545247, PMID:11087726, PMID:15591044). RPB4 facilitates CTD dephosphorylation by recruiting the phosphatases Ssu72 and Fcp1, promotes cotranscriptional 3′-end processing factor recruitment, enables gene-loop formation through bridging TFIIB and Ssu72, and supports transcriptional elongation via CCR4-Not complex association (PMID:25416796, PMID:18195044, PMID:31304538, PMID:25315781). Upon dissociation from Pol II, RPB4 accompanies mRNAs into the cytoplasm where its extensive post-translational modification repertoire regulates interactions with mRNA decay and translation initiation factors, coupling nuclear transcription to cytoplasmic mRNA metabolism (PMID:33440147, PMID:30359412).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 High

    Identifying RPB4 as a Pol II subunit that is dispensable for growth at permissive temperature but essential for full transcriptional activity established the concept of a conditionally required polymerase subunit.

    Evidence Gene cloning, deletion, and in vitro transcription assay in S. cerevisiae

    PMID:2674672

    Open questions at the time
    • No structural information on how Rpb4 integrates into the polymerase
    • Role at non-permissive temperatures unclear mechanistically
  2. 1998 High

    Structural and biophysical analyses revealed that Rpb4/Rpb7 reside in the DNA-binding cleft floor and stabilize pre-initiation complexes, answering how two 'dispensable' subunits contribute to transcription initiation.

    Evidence Electron microscopy difference mapping and surface plasmon resonance on yeast Pol II; in vitro transcription rescue with recombinant Rpb4

    PMID:9545247 PMID:9829926

    Open questions at the time
    • Atomic-resolution contacts between Rpb4/7 and the core unknown
    • Whether Rpb4 modification is needed in vivo unresolved
  3. 2000 High

    Demonstrating that the Rpb7 OB-fold binds single-stranded nucleic acids and that this binding is essential for a post-recruitment initiation step resolved the mechanistic function of the heterodimer beyond PIC stabilization.

    Evidence EMSA, OB-fold mutagenesis, and template competition in a reconstituted yeast transcription system

    PMID:11087726

    Open questions at the time
    • Identity of the RNA species engaged during initiation unknown
    • Contribution of Rpb4 versus Rpb7 to RNA binding not separated
  4. 2001 High

    Atomic structures of archaeal RPB4/RPB7 homologs provided the first molecular framework for how the heterodimer is organized, while functional studies showed Rpb4 is specifically required for activated—not constitutive—transcription.

    Evidence X-ray crystallography of M. jannaschii E/F complex; reporter assays and C-terminal deletion analysis of Rpb4 in S. cerevisiae

    PMID:11382749 PMID:11741548

    Open questions at the time
    • Human RPB4/7 structure not yet determined
    • Which activators require Rpb4 and why remains unclear
  5. 2002 High

    Discovery that Rpb4 directly recruits the CTD phosphatase Fcp1 and differentially modulates transcription-coupled DNA repair subpathways extended Rpb4's role beyond transcription initiation to elongation-coupled processes.

    Evidence Chemical cross-linking, GST pulldown, and CTD phosphatase assays in S. pombe; TCR assay with gene deletion epistasis in S. cerevisiae

    PMID:11839823 PMID:12411509

    Open questions at the time
    • Whether Rpb4 contacts Fcp1 directly in the context of the full polymerase remains unresolved
    • Structural basis for differential TCR subpathway regulation unknown
  6. 2004 High

    High-resolution crystal structures of the yeast Rpb4/7 heterodimer and complete 12-subunit Pol II defined the atomic interface between the heterodimer and the core, explaining temperature-sensitive dissociation and the Rpb6 contact point.

    Evidence X-ray crystallography at 2.3 Å (Rpb4/7) and 3.8 Å (12-subunit Pol II); conditional Rpb6 mutation analysis

    PMID:12697831 PMID:15591044

    Open questions at the time
    • Dynamic association/dissociation kinetics in vivo not measured
    • Role of Rpb6 flexibility in regulating Rpb4/7 release uncharacterized
  7. 2005 High

    Determination of the human RPB4/RPB7 crystal structure and mapping of the conserved RNA-binding surface on RPB7 confirmed structural conservation from archaea to humans and validated the RNA-binding mechanism.

    Evidence X-ray crystallography at 2.7 Å, site-directed mutagenesis, and EMSA on human RPB4/RPB7

    PMID:16282592

    Open questions at the time
    • No structure of human RPB4/7 in the context of the full human Pol II
    • Which RNA species are bound by human RPB7 in vivo unknown
  8. 2008 High

    Genome-wide ChIP-chip showing Rpb7 occupancy mirrors core subunit occupancy, combined with evidence that Rpb4 recruits 3′-end processing factors, established that Rpb4/7 functions throughout the transcription cycle—not just at initiation.

    Evidence ChIP-chip tiling arrays comparing Rpb7 and Rpb3 genome-wide; ChIP and poly(A)-site mapping at individual genes in rpb4Δ

    PMID:18195044 PMID:18667430

    Open questions at the time
    • Whether 3′-end processing factor recruitment is through direct Rpb4 contacts or indirect
    • Gene-specificity of 3′-end processing defects not fully explored
  9. 2009 High

    Reconstitution of archaeal RNAP with and without F/E demonstrated that the RPB4/7 module stimulates polymerase processivity and reduces pausing, establishing a direct elongation-promoting function partially dependent on RNA binding.

    Evidence Reconstituted in vitro transcription with recombinant archaeal RNAP and mutant F/E variants

    PMID:19906731

    Open questions at the time
    • Whether eukaryotic Rpb4/7 exerts the same processivity stimulation in a fully reconstituted system untested
    • RNA-binding-independent component of processivity stimulation uncharacterized
  10. 2013 Medium

    Quantitative proteomics revealed that Rpb4/7 dissociates from elongating Pol II upon Ser2P CTD phosphorylation-dependent recruitment of elongation factors, establishing that the heterodimer is not a permanent fixture during elongation.

    Evidence Quantitative mass spectrometry of RNAPII purified via Rpb7 versus core subunit tags

    PMID:23418395

    Open questions at the time
    • Which specific elongation factors trigger dissociation not identified
    • Whether dissociation is regulated or stochastic in vivo unclear
  11. 2014 High

    Metabolic labeling with an Rpb2–Rpb4 fusion rescue, CTD phosphorylation analysis, and CCR4-Not interaction studies collectively established that Rpb4's primary function is in nuclear mRNA synthesis, that it controls CTD phosphorylation by recruiting Ssu72 and Fcp1, and that it enables CCR4-Not-mediated elongation complex reactivation.

    Evidence cDTA metabolic labeling, Rpb2-Rpb4 fusion rescue, ChIP for CTD marks, Western blotting, in vitro elongation assays with reconstituted complexes

    PMID:24802753 PMID:25315781 PMID:25416796

    Open questions at the time
    • Structural basis for Rpb4-mediated phosphatase recruitment unknown
    • Mechanism by which Rpb4/7 enables CCR4-Not association not defined at the molecular level
  12. 2019 Medium

    Demonstrating that Rpb4 is required for gene loop formation via TFIIB–Ssu72 bridging answered how Pol II is recycled from terminator to promoter and linked Rpb4 to transcription reinitiation.

    Evidence Chromosome conformation capture (3C), TFIIB–Ssu72 interaction assays, and transcription termination assays in rpb4Δ

    PMID:31304538

    Open questions at the time
    • Whether gene looping occurs at all genes or a subset is unresolved
    • Direct protein–protein contacts mediating the TFIIB–Rpb4–Ssu72 bridge not structurally defined
  13. 2021 Medium

    Mass spectrometry-based mapping of >100 PTM combinations on Rpb4/7 that change through the mRNA life cycle revealed how post-translational modification regulates the handoff between Pol II, translation initiation factors, and mRNA decay machinery.

    Evidence MS-based PTM mapping, PTM-site mutant analysis, co-immunoprecipitation with eIF3 and Pat1

    PMID:33440147

    Open questions at the time
    • Enzymes responsible for most Rpb4/7 modifications not identified
    • Whether PTM patterns are conserved in human RPB4 unknown
  14. 2022 Medium

    Two studies linked RPB4 to viral exploitation and upstream phosphatase-regulated assembly: influenza PB2 directly binds human RPB4 to position the viral polymerase near nascent host mRNA caps, while the CTD phosphatase Rtr1 controls Rpb4 incorporation into Pol II and downstream mRNA imprinting.

    Evidence Binary complementation assay, co-IP, and mutagenesis for PB2–RPB4 interaction; ChIP and mRNA stability assays for Rtr1–Rpb4 link

    PMID:35216121 PMID:35336925

    Open questions at the time
    • Structural basis of PB2–RPB4 interaction not determined
    • Whether Rtr1-dependent Rpb4 incorporation is conserved in mammalian cells untested
    • Whether other viral polymerases exploit RPB4 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for Rpb4-mediated recruitment of CTD phosphatases and 3′-end processing factors to the human Pol II elongation complex, the identity of the enzymes that install and remove Rpb4/7 post-translational modifications, and whether dynamic Rpb4/7 dissociation during elongation is a regulated signaling event or a passive consequence of conformational changes.
  • No cryo-EM structure of human Pol II elongation complex with or without RPB4/7 bound to accessory factors
  • Writers and erasers of Rpb4/7 PTMs unidentified
  • Mechanism governing regulated versus stochastic Rpb4/7 dissociation in vivo unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 1
Partners
CTDP1POLR2BPOLR2FPOLR2GSSU72TFIIB
Complex memberships
RNA polymerase IIRpb4/Rpb7 heterodimer

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 RPB4 (Rpb4) encodes the fourth-largest RNA polymerase II subunit in S. cerevisiae; deletion of RPB4 produces heat- and cold-sensitive cells and RNA polymerase II lacking Rpb4 shows markedly reduced activity in vitro, demonstrating that Rpb4 is essential for normal Pol II activity and cell viability over a wide temperature range, though not strictly required for mRNA synthesis or enzyme assembly at permissive temperatures. Gene cloning/sequencing, gene deletion, in vitro transcription assay Molecular and cellular biology High 2674672
1998 Rpb4 and Rpb7 form part of the floor of the DNA-binding cleft in yeast RNA polymerase II and stabilize a minimal pre-initiation complex containing promoter DNA, TBP, TFIIB, and polymerase, as shown by 3D structural comparison and surface plasmon resonance; these subunits are proposed to couple DNA entry into the active center cleft to cleft closure. Electron microscopy (3D structure), difference mapping, surface plasmon resonance The EMBO journal High 9545247
1998 Rpb4 is required for RNA polymerase II enzymatic activity at temperature extremes (10°C and 35°C) but not at moderate temperature (23°C); recombinant Rpb4 produced in E. coli can rescue Pol II activity at non-optimal temperatures when added to cell extracts, indicating no post-translational modification of Rpb4 is required for its functional association with other Pol II subunits. In vitro transcription assay (promoter-independent), immunoprecipitation, sucrose gradient, recombinant protein rescue Journal of bacteriology High 9829926
1999 Rpb7 can interact with and support Pol II transcription independently of Rpb4 under some stress conditions when overexpressed; a major role of Rpb4 is to augment the interaction of Rpb7 with the Pol II core, as demonstrated by reciprocal co-immunoprecipitation showing stable Rpb7 association with Pol IIΔ4. Genetic suppression screen, reciprocal co-immunoprecipitation, growth/transcription assays Molecular and cellular biology High 10082533
2000 The Rpb4-Rpb7 heterodimeric subcomplex of yeast Pol II binds single-stranded DNA and RNA through an OB-fold motif in Rpb7; Rpb4-Rpb7 is not required for stable recruitment of polymerase to preinitiation complexes but mediates an essential post-recruitment step in transcription initiation; mutations in the OB-fold that abolish nucleic acid binding also destroy transcription activity. Template competition assay, electrophoretic mobility shift assay, OB-fold deletion mutagenesis, reconstituted transcription system The Journal of biological chemistry High 11087726
2001 Crystal structure of the archaeal homologs of RPB7 and RPB4 (subunits E and F from Methanococcus jannaschii) determined at atomic resolution; subunit E has an elongated two-domain structure with two potential RNA-binding motifs, and the smaller F subunit wraps around one side of E at the domain interface; a model is proposed in which the RNA-binding face of RPB7 interacts with nascent RNA transcript. X-ray crystallography Molecular cell High 11741548
2001 Rpb4 is required for transcriptional activation from a subset of promoters in S. cerevisiae; constitutive transcription is largely unaffected in rpb4Δ, but activation is severely compromised; the C-terminal 24 amino acids of Rpb4 are required for this activation function, and Rpb4 and Rpb7 play independent roles in transcriptional regulation. Reporter gene assays, Northern blotting, domain deletion analysis, rpb4Δ mutant analysis The Journal of biological chemistry Medium 11382749
2002 Formation of a Fcp1/TFIIF/RNA polymerase II complex in S. pombe involves direct interaction between the CTD-phosphatase Fcp1 and the Rpb4 subunit of Pol II, identified by chemical cross-linking, GST pulldown, and affinity chromatography; repression of rpb4 expression results in less Fcp1 in the Pol II complex and increased Rpb1 CTD phosphorylation. Immunoaffinity purification, in vitro CTD-phosphatase assay, chemical cross-linking, GST pulldown, affinity chromatography, thiamine-regulated shut-off Molecular and cellular biology High 11839823
2002 Rpb4, a non-essential subunit of RNA polymerase II, plays a dual role in transcription-coupled DNA repair (TCR) in S. cerevisiae: it suppresses the Rpb9-mediated TCR subpathway while facilitating the Rad26-mediated TCR subpathway, demonstrating that Rpb4 regulates distinct TCR subpathways differentially. TCR assay using strand-specific primer extension after UV irradiation, gene deletion epistasis analysis The EMBO journal High 12411509
2003 A conditional mutation (Q100R) in the shared Rpb6 subunit causes selective loss of Rpb4 and Rpb7 from RNA polymerase II, and interaction experiments support a direct association between Rpb6 and Rpb4, indicating that Rpb6 is a key contact point between the Rpb4/Rpb7 subcomplex and the Pol II core. Conditional mutation analysis, Pol II purification, interaction/pulldown experiments Molecular and cellular biology Medium 12697831
2004 X-ray structure of the yeast Rpb4/7 subcomplex determined at 2.3 Å resolution and combined with the 10-subunit core to refine the complete 12-subunit Pol II structure at 3.8 Å; the core-Rpb4/7 interaction involves formation of an alpha-helix in the linker of Rpb1 and folding of the conserved Rpb7 tip loop; details of the interface explain facilitated Rpb4/7 dissociation in temperature-sensitive mutants and specific assembly of Pol I A43/14 counterpart. X-ray crystallography (2.3 Å and 3.8 Å) The Journal of biological chemistry High 15591044
2005 Crystal structure of the human Rpb4/Rpb7 heterodimer determined at 2.7 Å resolution; biochemical studies with site-directed mutagenesis and EMSA identified an elongated surface region on Rpb7 (spanning the OB-fold nucleic acid binding face including the B4-B5 loop and N-terminal domain) responsible for RNA binding, conserved between human Rpb7 and archaeal subunit E. X-ray crystallography, site-directed mutagenesis, electrophoretic mobility shift assay (EMSA) Nucleic acids research High 16282592
2007 The Rpb4/7 subcomplex associates with the Pol II core through two crucial interaction points: the N-terminal RNP-like domain of Rpb7 and the partially ordered N-terminal region of Rpb4 (which contacts Rpb2); mutations in the Rpb7 RNP domain increase dependence on Rpb4 for polymerase association, as shown by complementation analysis and RNA polymerase pulldown assays. Site-directed mutagenesis, complementation analysis, RNA polymerase pulldown assay The Journal of biological chemistry Medium 18056993
2008 Rpb4 contributes to cotranscriptional recruitment of 3'-end processing factors to Pol II; loss of Rpb4 reduces Pol II levels near 3' ends of multiple mRNA genes, decreases association of 3'-end processing factors, and alters polyadenylation site usage at the RNA14 gene, as shown by chromatin immunoprecipitation. Chromatin immunoprecipitation (ChIP), polyadenylation site mapping Molecular and cellular biology Medium 18195044
2008 Genome-wide ChIP-chip analysis shows that Rpb7 (and by inference the Rpb4/7 subcomplex) occupancy profiles across the yeast genome are essentially identical to those of the core subunit Rpb3, demonstrating that the complete Pol II including Rpb4/7 associates with DNA in vivo throughout transcribed genes. Chromatin immunoprecipitation coupled to high-resolution tiling microarray (ChIP-chip) The Journal of biological chemistry High 18667430
2009 The archaeal F/E complex (homolog of RPB4/7) greatly stimulates RNAP processivity, enhances full-length transcript formation, reduces pausing, and increases transcription termination at weak termination signals in a wholly recombinant archaeal system; these activities correlate with the RNA-binding properties of F/E, though a second RNA-binding-independent component also contributes. Reconstituted in vitro transcription with recombinant archaeal RNAP, mutant F/E variants, synthetic nucleic acid scaffolds Nucleic acids research High 19906731
2013 Rpb4 and Rpb7 dissociate from RNA polymerase II upon interaction with specific transcriptional elongation-associated proteins recruited to the hyperphosphorylated (Ser2P) CTD; RNAPII isolated through Rpb7 is depleted in Ser2 CTD phosphorylation, indicating that Rpb4/7 are dispensable during specific stages of transcriptional elongation. Quantitative proteomics (mass spectrometry), affinity purification of RNAPII through Rpb7 Molecular & cellular proteomics Medium 23418395
2014 Rpb4 mainly functions in nuclear mRNA synthesis by Pol II; rpb4Δ causes a drastic defect in mRNA synthesis compensated by down-regulation of mRNA degradation (mRNA level buffering); covalent fusion of Rpb4 to core subunit Rpb2 largely restores mRNA synthesis and degradation defects, establishing Rpb4 as a bona fide Pol II core subunit primarily acting in mRNA synthesis rather than cytoplasmic mRNA degradation. Metabolic RNA labeling, comparative Dynamic Transcriptome Analysis (cDTA), Rpb2-Rpb4 fusion rescue experiment The Journal of biological chemistry High 24802753
2014 The Rpb4/7 heterodimer controls phosphorylation of the Rpb1 CTD in S. cerevisiae; deletion of RPB4 increases phosphorylation of Ser2, Ser5, Ser7, and Thr4 on the CTD; Rpb4 facilitates association, recruitment, and/or accessibility of CTD phosphatases Ssu72 (Ser5P) and Fcp1 (Ser2P and Thr4P) to the CTD. Genetic interactions (RPB4 with CTD kinases/phosphatases), ChIP, Western blotting for CTD phosphorylation marks Nucleic acids research High 25416796
2014 The Rpb4/7 module of RNA polymerase II is required for the CCR4-Not complex to associate with elongation complexes and stimulate transcription elongation by reactivating arrested elongation complexes, suggesting a mechanism by which Rpb4/7 coordinates mRNA synthesis and decay. In vitro elongation assay with reconstituted transcription complexes, genetic and biochemical analysis of Ccr4-Not-Pol II interaction The Journal of biological chemistry Medium 25315781
2018 Dissociation of Rpb4 from Pol II is required for normal mRNA decay and cellular adaptability; an Rpb2-Rpb4 fusion protein that prevents free Rpb4 release adversely affects mRNA decay and stress response; free Rpb4 binds mRNAs and polysomes in the cytoplasm, and the fusion Pol II can also bind poly(A)+ mRNAs via Rpb7 as a compensatory mechanism. Rpb2-Rpb4 fusion protein analysis, mRNA decay assays, polysome fractionation, mRNA binding (RIP) PloS one Medium 30359412
2019 RNAPII plays a direct role in gene loop formation through the Rpb4 subunit; 3C analysis shows gene looping is abolished in rpb4Δ mutants without a transcription termination defect; Rpb4 facilitates the interaction between TFIIB and Ssu72, which is critical for gene loop formation and promotes RNAPII transfer from terminator to promoter for reinitiation. Chromosome conformation capture (3C), genetic interaction analysis, transcription termination assays, TFIIB-Ssu72 interaction assay Nucleic acids research Medium 31304538
2021 Rpb4/7 can undergo more than 100 combinations of post-translational modifications (PTMs); the PTM repertoire of Rpb4/7 changes as the mRNA/Rpb4/7 complex progresses through different stages of the mRNA life cycle; specific PTM mutants affect Rpb4 interactions with key regulators (Pol II, eIF3, Pat1) and disrupt the balance between mRNA synthesis and decay. Mass spectrometry-based PTM mapping, PTM mutant analysis, co-immunoprecipitation, mRNA synthesis/decay assays Cell reports Medium 33440147
2022 The N-terminal domain of the influenza A PB2 subunit directly interacts with human RPB4 (POLR2D), as confirmed by binary complementation assay and co-immunoprecipitation; the N-half domain of RPB4 is critical for this interaction; point mutations at conserved positions in the PB2 N-third domain cause strong transcriptional activity defects, suggesting the PB2-RPB4 interaction positions FluPol near the 5'-end of nascent host mRNA for cap-snatching. Binary complementation assay, co-immunoprecipitation, site-directed mutagenesis, transcription activity assay Viruses Medium 35336925
2022 Association of Rpb4 with RNA polymerase II depends on the CTD Ser5P phosphatase Rtr1; deletion of RTR1 alters Pol II assembly by increasing the amount of chromatin-associated Pol II lacking Rpb4, which decreases Rpb4-mRNA imprinting and consequently increases mRNA stability, linking Rtr1-mediated CTD dephosphorylation to Rpb4/7 incorporation into Pol II and downstream mRNA decay regulation. Co-immunoprecipitation, ChIP, mRNA stability assays, Pol II assembly analysis International journal of molecular sciences Medium 35216121
2025 Cryo-EM structures of native metazoan (Drosophila) transcription complexes revealed the first structure of a native Rpb4/Rpb7 stalk-less Pol II elongation complex, demonstrating that diverse elongation complexes lacking the Rpb4/7 stalk are present during active transcription in vivo. Cryo-EM of native transcription complexes, FLAG-affinity purification, proteomics bioRxivpreprint Low bio_10.1101_2025.02.03.636274

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1998 A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 1086 9491887
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1997 Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA (New York, N.Y.) 869 9409616
1996 The general transcription factors of RNA polymerase II. Genes & development 849 8946909
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2002 Comprehensive proteomic analysis of the human spliceosome. Nature 725 12226669
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2000 Architecture of RNA polymerase II and implications for the transcription mechanism. Science (New York, N.Y.) 452 10784442
2005 Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 443 16239144
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
1999 HIV-1 tat transcriptional activity is regulated by acetylation. The EMBO journal 361 10545121
2010 HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Molecular cell 336 20471948
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2012 HIV-1 reverse transcription. Cold Spring Harbor perspectives in medicine 315 23028129
1995 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. Journal of virology 311 7853496
2011 Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 281 21729782
2004 A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molecular cell 265 15175163
2012 The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation. Nucleic acids research 254 23087374
1996 Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain. Nature 245 8934526
2000 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. Molecular and cellular biology 227 10866664
2004 Structures of complete RNA polymerase II and its subcomplex, Rpb4/7. The Journal of biological chemistry 186 15591044
1989 RNA polymerase II subunit RPB4 is essential for high- and low-temperature yeast cell growth. Molecular and cellular biology 166 2674672
2009 NRPD4, a protein related to the RPB4 subunit of RNA polymerase II, is a component of RNA polymerases IV and V and is required for RNA-directed DNA methylation. Genes & development 115 19204117
2002 Rpb4 and Rpb9 mediate subpathways of transcription-coupled DNA repair in Saccharomyces cerevisiae. The EMBO journal 109 12411509
2001 Structure of an archaeal homolog of the eukaryotic RNA polymerase II RPB4/RPB7 complex. Molecular cell 90 11741548
2004 Rpb4 and Rpb7: subunits of RNA polymerase II and beyond. Trends in biochemical sciences 87 15544954
2002 Formation of a carboxy-terminal domain phosphatase (Fcp1)/TFIIF/RNA polymerase II (pol II) complex in Schizosaccharomyces pombe involves direct interaction between Fcp1 and the Rpb4 subunit of pol II. Molecular and cellular biology 83 11839823
2000 Dissociable Rpb4-Rpb7 subassembly of rna polymerase II binds to single-strand nucleic acid and mediates a post-recruitment step in transcription initiation. The Journal of biological chemistry 73 11087726
2008 The Rpb4 subunit of RNA polymerase II contributes to cotranscriptional recruitment of 3' processing factors. Molecular and cellular biology 63 18195044
2005 Crystal structure and RNA binding of the Rpb4/Rpb7 subunits of human RNA polymerase II. Nucleic acids research 59 16282592
1998 Structure of wild-type yeast RNA polymerase II and location of Rpb4 and Rpb7. The EMBO journal 56 9545247
1999 Rpb7 can interact with RNA polymerase II and support transcription during some stresses independently of Rpb4. Molecular and cellular biology 53 10082533
1998 Rpb4, a subunit of RNA polymerase II, enables the enzyme to transcribe at temperature extremes in vitro. Journal of bacteriology 53 9829926
2009 Molecular mechanisms of RNA polymerase--the F/E (RPB4/7) complex is required for high processivity in vitro. Nucleic acids research 48 19906731
2000 Archaeal RNA polymerase subunits F and P are bona fide homologs of eukaryotic RPB4 and RPB12. Nucleic acids research 47 11058130
1999 The Rpb4 subunit of fission yeast Schizosaccharomyces pombe RNA polymerase II is essential for cell viability and similar in structure to the corresponding subunits of higher eukaryotes. Molecular and cellular biology 47 10523639
2002 The A14-A43 heterodimer subunit in yeast RNA pol I and their relationship to Rpb4-Rpb7 pol II subunits. Proceedings of the National Academy of Sciences of the United States of America 43 12407181
2015 Contribution of PRS3, RPB4 and ZWF1 to the resistance of industrial Saccharomyces cerevisiae CCUG53310 and PE-2 strains to lignocellulosic hydrolysate-derived inhibitors. Bioresource technology 42 25974617
1993 A growth rate-limiting process in the last growth phase of the yeast life cycle involves RPB4, a subunit of RNA polymerase II. Journal of bacteriology 39 8407810
2008 Genome-associated RNA polymerase II includes the dissociable Rpb4/7 subcomplex. The Journal of biological chemistry 38 18667430
2003 An Rpb4/Rpb7-like complex in yeast RNA polymerase III contains the orthologue of mammalian CGRP-RCP. Molecular and cellular biology 38 12482973
2013 Quantitative proteomics demonstrates that the RNA polymerase II subunits Rpb4 and Rpb7 dissociate during transcriptional elongation. Molecular & cellular proteomics : MCP 37 23418395
1998 Two small subunits in Arabidopsis RNA polymerase II are related to yeast RPB4 and RPB7 and interact with one another. The Journal of biological chemistry 35 9488692
2014 Rpb4 subunit functions mainly in mRNA synthesis by RNA polymerase II. The Journal of biological chemistry 34 24802753
2019 RNA polymerase II plays an active role in the formation of gene loops through the Rpb4 subunit. Nucleic acids research 33 31304538
2001 Rpb4, a non-essential subunit of core RNA polymerase II of Saccharomyces cerevisiae is important for activated transcription of a subset of genes. The Journal of biological chemistry 33 11382749
2005 Rpb4 and Rpb7: a sub-complex integral to multi-subunit RNA polymerases performs a multitude of functions. IUBMB life 31 16036568
2003 Loss of the Rpb4/Rpb7 subcomplex in a mutant form of the Rpb6 subunit shared by RNA polymerases I, II, and III. Molecular and cellular biology 31 12697831
2001 Deletion of the RNA polymerase subunit RPB4 acts as a global, not stress-specific, shut-off switch for RNA polymerase II transcription at high temperatures. The Journal of biological chemistry 31 11577101
2014 The Rpb4/7 module of RNA polymerase II is required for carbon catabolite repressor protein 4-negative on TATA (Ccr4-not) complex to promote elongation. The Journal of biological chemistry 29 25315781
2014 Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation. Nucleic acids research 29 25416796
2010 Cycling through transcription with the RNA polymerase F/E (RPB4/7) complex: structure, function and evolution of archaeal RNA polymerase. Research in microbiology 26 20863887
2008 Genomewide recruitment analysis of Rpb4, a subunit of polymerase II in Saccharomyces cerevisiae, reveals its involvement in transcription elongation. Eukaryotic cell 25 18441121
2009 RNAP subunits F/E (RPB4/7) are stably associated with archaeal RNA polymerase: using fluorescence anisotropy to monitor RNAP assembly in vitro. The Biochemical journal 21 19492989
2012 Rpb4 and Rpb7: multifunctional subunits of RNA polymerase II. Critical reviews in microbiology 19 22917057
2006 The fission yeast Rpb4 subunit of RNA polymerase II plays a specialized role in cell separation. Molecular genetics and genomics : MGG 18 16972065
2016 Rpb1 foot mutations demonstrate a major role of Rpb4 in mRNA stability during stress situations in yeast. Biochimica et biophysica acta 17 27001033
2001 Multiple cellular processes affected by the absence of the Rpb4 subunit of RNA polymerase II contribute to the deficiency in the stress response of the yeast rpb4(delta) mutant. Molecular & general genetics : MGG 17 11254123
2009 The Med8 mediator subunit interacts with the Rpb4 subunit of RNA polymerase II and Ace2 transcriptional activator in Schizosaccharomyces pombe. FEBS letters 13 19720063
2003 The conserved and non-conserved regions of Rpb4 are involved in multiple phenotypes in Saccharomyces cerevisiae. The Journal of biological chemistry 12 14530281
2021 Numerous Post-translational Modifications of RNA Polymerase II Subunit Rpb4/7 Link Transcription to Post-transcriptional Mechanisms. Cell reports 11 33440147
2018 Dissociation of Rpb4 from RNA polymerase II is important for yeast functionality. PloS one 11 30359412
2020 Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast. RNA biology 9 33094674
2007 Unstructured N terminus of the RNA polymerase II subunit Rpb4 contributes to the interaction of Rpb4.Rpb7 subcomplex with the core RNA polymerase II of Saccharomyces cerevisiae. The Journal of biological chemistry 8 18056993
2022 The Influenza Virus RNA-Polymerase and the Host RNA-Polymerase II: RPB4 Is Targeted by a PB2 Domain That Is Involved in Viral Transcription. Viruses 7 35336925
2022 The Association of Rpb4 with RNA Polymerase II Depends on CTD Ser5P Phosphatase Rtr1 and Influences mRNA Decay in Saccharomyces cerevisiae. International journal of molecular sciences 4 35216121
2019 A comparative study of the proteome regulated by the Rpb4 and Rpb7 subunits of RNA polymerase II in fission yeast. Journal of proteomics 4 30862564
2013 The RNA polymerase II Rpb4/7 subcomplex regulates cellular lifespan through an mRNA decay process. Biochemical and biophysical research communications 4 24358479
2009 The dissociable RPB4 subunit of RNA Pol II has vital functions in Drosophila. Molecular genetics and genomics : MGG 4 19921261
2005 Mapping the interaction site of Rpb4 and Rpb7 subunits of RNA polymerase II in Saccharomyces cerevisiae. Biochemical and biophysical research communications 3 15913559
2014 Involvement of S. cerevisiae Rpb4 in subset of pathways related to transcription elongation. Gene 1 24780862
2008 RAM pathway contributes to Rpb4 dependent pseudohyphal differentiation in Saccharomyces cerevisiae. Fungal genetics and biology : FG & B 1 18687406