Affinage

POLR2I

DNA-directed RNA polymerase II subunit RPB9 · UniProt P36954

Round 2 corrected
Length
125 aa
Mass
14.5 kDa
Annotated
2026-04-28
55 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR2I (Rpb9) is a conserved, non-catalytic subunit of RNA polymerase II that occupies the downstream DNA-gripping jaw of the enzyme and exerts broad regulatory control over transcription initiation accuracy, elongation fidelity, and coupled DNA repair. Rpb9 ensures correct transcription start site selection through functional interactions with the general transcription factors TFIIB and TFIIF (PMID:7883169, PMID:8692696, PMID:14522989), and it promotes transcriptional fidelity by anchoring Rpb1 α-helix 21 to modulate trigger loop dynamics, thereby slowing mismatch extension and facilitating TFIIS-mediated proofreading (PMID:19439405, PMID:27226557, PMID:24099331). Rpb9 mediates a Rad26-independent subpathway of transcription-coupled nucleotide excision repair via its Zn1/linker domains and separately promotes UV-induced ubiquitylation and proteasomal degradation of Rpb1 via its Zn2 domain (PMID:12411509, PMID:17452455). Additional roles include recruiting the Integrator complex to piRNA genes for transcriptional termination in C. elegans germline (PMID:33533030), activating ATG1/ULK1 transcription to regulate autophagy through Gcn4-dependent promoter binding (PMID:36102592), and supporting normal cardiac morphogenesis and left-right asymmetry in zebrafish (PMID:41198546).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Establishing that Rpb9 is a non-essential but growth-important Pol II subunit answered whether every polymerase subunit is required for viability and opened genetic dissection of its specialized roles.

    Evidence Gene deletion in S. cerevisiae with temperature-sensitivity growth assays

    PMID:1918023

    Open questions at the time
    • Molecular function of Rpb9 within the polymerase was unknown
    • No structural information
  2. 1995 High

    Demonstrating that Rpb9 is required for accurate transcription start site selection — and that reconstitution with recombinant Rpb9 rescues the defect — established Rpb9's first defined molecular function and showed the metal-binding domain is critical.

    Evidence In vitro reconstituted transcription with purified Δ9 Pol II and recombinant Rpb9, in vivo promoter mapping

    PMID:7883169

    Open questions at the time
    • Mechanism of start site selection by Rpb9 was unknown
    • Interaction partners mediating this function not identified
  3. 1996 High

    Genetic suppression between Rpb9 and TFIIB identified their functional interaction in start site selection, revealing that Rpb9 operates through the general transcription machinery rather than acting alone.

    Evidence Genetic suppressor screen in S. cerevisiae linking rpb9 alleles to TFIIB (sua7) mutations

    PMID:8692696

    Open questions at the time
    • Whether the interaction is direct or mediated by other factors
    • Role of other GTFs not tested
  4. 1997 High

    Reconstitution experiments revealed that Rpb9 regulates elongation through DNA arrest sites and is required for TFIIS-stimulated read-through, establishing a second major function beyond initiation.

    Evidence In vitro transcription elongation assays with purified Δ9 Pol II reconstituted with recombinant Rpb9 and TFIIS

    PMID:9169440

    Open questions at the time
    • Structural basis of Rpb9-TFIIS cooperation unknown
    • In vivo relevance of elongation role not yet demonstrated
  5. 2000 High

    The 3 Å crystal structure of yeast Pol II placed Rpb9 in the downstream DNA jaw with Rpb1 and Rpb5, providing the first structural framework explaining how a peripheral subunit influences both initiation and elongation.

    Evidence X-ray crystallography of 10-subunit yeast RNA polymerase II

    PMID:10784442

    Open questions at the time
    • Structure did not resolve dynamics of Rpb9 during transcription cycle
    • Interactions with GTFs not structurally visualized
  6. 2000 High

    Systematic mutagenesis of 20 Rpb9 variants separated the N-terminal zinc ribbon (initiation) from the C-terminal zinc ribbon acidic loop (elongation) and identified the linker as the Pol II interaction region, assigning domain-specific functions.

    Evidence In vivo 6-azauracil sensitivity, in vitro transcription reconstitution, domain mutagenesis

    PMID:10644677 PMID:10938084

    Open questions at the time
    • Structural basis of domain-specific functions not resolved
    • Interaction with TFIIF not yet tested
  7. 2002 High

    Double-deletion analysis established that Rpb9 mediates a Rad26-independent subpathway of transcription-coupled repair, revealing that eukaryotic TCR has two parallel mechanisms rather than one.

    Evidence UV damage repair mapping with single and double mutants of RPB9 and RAD26 in S. cerevisiae

    PMID:12411509

    Open questions at the time
    • Mechanism by which Rpb9 promotes repair factor recruitment unknown
    • Whether this pathway is conserved in mammals
  8. 2002 High

    Physical interaction between Rpb9 and TFIIE subunit Tfa1 revealed Rpb9 as a docking site for TFIIE on Pol II, and synthetic lethality with Elongator/SAGA linked Rpb9 to histone acetylation pathways.

    Evidence Two-hybrid and co-immunoprecipitation in S. cerevisiae; genetic synthetic lethality analysis

    PMID:11779853

    Open questions at the time
    • Functional consequence of TFIIE recruitment via Rpb9 on transcription not fully delineated
    • Structural basis of Rpb9-Tfa1 interaction lacking
  9. 2003 High

    Demonstrating that Rpb9 is required for proper Pol II–TFIIF interaction resolved the mechanistic basis of Rpb9's start site selection function, linking it to TFIIF positioning on the enzyme.

    Evidence Reconstituted transcription with purified TFIIF and Δ9 Pol II, gel mobility shift assays

    PMID:14522989

    Open questions at the time
    • Whether Rpb9-TFIIF interaction is direct or mediated by conformational changes in Pol II
  10. 2006 High

    In vivo fidelity assays with cDNA sequencing proved that Rpb9 is the primary Pol II subunit ensuring transcriptional fidelity, with loss causing substitutions and insertions — a more severe phenotype than TFIIS deletion.

    Evidence Canavanine-sensitivity transcription fidelity assay, cDNA sequencing of error products in S. cerevisiae

    PMID:16492753

    Open questions at the time
    • Kinetic mechanism of fidelity control not yet defined
    • Relationship between fidelity and elongation/arrest functions unclear
  11. 2006 High

    Domain analysis linking Rpb9's Zn1/linker to both elongation and TCR — while Zn2 was dispensable for both — unified these two functions mechanistically and showed that TCR depends on elongation competence.

    Evidence Domain deletion mutagenesis with UV repair assays and genetic epistasis with elongation factor mutants

    PMID:17030604

    Open questions at the time
    • Molecular contacts between Rpb9 domains and repair machinery not identified
  12. 2007 High

    Identification of Rpb9's Zn2 domain as essential for UV-induced Rpb1 ubiquitylation and proteasomal degradation established a third, separable function for Rpb9 in the DNA damage response distinct from TCR.

    Evidence UV irradiation, Rpb1 ubiquitylation Western blots, domain mutagenesis, proteasome inhibitor treatment in S. cerevisiae

    PMID:17452455

    Open questions at the time
    • E3 ligase responsible for Rpb9-dependent Rpb1 ubiquitylation not identified
    • Conservation in mammalian UV response unknown
  13. 2009 High

    Pre-steady state kinetics revealed that Rpb9 controls fidelity by delaying NTP sequestration prior to phosphodiester bond formation, providing the first kinetic mechanism for a polymerase subunit's role in nucleotide selectivity.

    Evidence Pre-steady state kinetic analysis of NTP incorporation and misincorporation with Δ9 Pol II in vitro

    PMID:19439405

    Open questions at the time
    • How Rpb9, located distantly from the active site, communicates with the active center was unknown
  14. 2013 High

    Dissection of proofreading showed Rpb9 slows mismatch extension and facilitates TFIIS-mediated cleavage of misincorporated nucleotides, but does not affect initial NTP discrimination — separating Rpb9's fidelity contributions into two distinct post-incorporation steps.

    Evidence In vitro fidelity assays with defined mismatched elongation complexes and TFIIS cleavage assays

    PMID:24099331

    Open questions at the time
    • Structural basis for how Rpb9 promotes the cleavage-competent conformation not resolved
  15. 2016 High

    Demonstrating that Rpb9 indirectly modulates trigger loop mobility by anchoring Rpb1 α-helix 21 resolved the long-standing question of how a peripheral subunit influences catalysis at the distant active center.

    Evidence α-amanitin inhibition, genetic suppressor analysis with rpb1-G730D (α-helix 21), epistasis with fast rpb1 alleles

    PMID:27226557

    Open questions at the time
    • High-resolution structural visualization of Rpb9–α21–TL conformational coupling not achieved
    • Whether this mechanism operates identically in mammals
  16. 2018 Medium

    Synthetic lethality between Rpb9 deletion and histone H3 lysine mutations revealed that Rpb9 cooperates with H3 acetylation to maintain DNA damage checkpoint activation and genome stability.

    Evidence Genetic interaction analysis, immunoblot for γH2A and Rad53, flow cytometry for chromosome segregation in S. cerevisiae

    PMID:29440683

    Open questions at the time
    • Whether Rpb9 directly influences histone modification or acts indirectly through transcription
    • Single-lab observation awaiting independent confirmation
  17. 2021 High

    Discovery that C. elegans RPB-9 recruits the Integrator complex to piRNA genes for transcriptional termination expanded Rpb9's functional repertoire beyond general transcription to non-coding RNA biogenesis and germline gene silencing.

    Evidence Genetic mutant analysis, co-immunoprecipitation for Integrator recruitment, piRNA sequencing, reporter silencing in C. elegans germline

    PMID:33533030

    Open questions at the time
    • Whether Rpb9-Integrator interaction is conserved in mammals
    • Structural basis of Rpb9-Integrator interaction unknown
  18. 2022 High

    Genome-wide screening and ChIP identified Rpb9 as a direct transcriptional activator of ATG1/ULK1 through Gcn4-mediated promoter binding, linking a Pol II subunit to autophagy regulation — a function conserved in mammals.

    Evidence Yeast knockout screen, ChIP at ATG1 promoter, autophagy flux assays, mammalian POLR2I knockdown with ULK1 readouts

    PMID:36102592

    Open questions at the time
    • Whether this is a moonlighting function independent of core Pol II or occurs in the context of the holoenzyme
    • Upstream signals regulating Rpb9-Gcn4 cooperation at the ATG1 promoter
  19. 2025 Medium

    Zebrafish polr2i knockdown causing cardiac malformations, disrupted left-right asymmetry, and impaired myocardial mitochondrial quality extended Rpb9's developmental roles to vertebrate organogenesis.

    Evidence Morpholino knockdown with mRNA rescue in zebrafish, cardiac function measurements, fluorescent reporter imaging

    PMID:41198546

    Open questions at the time
    • Morpholino approach requires genetic mutant confirmation
    • Whether cardiac phenotype reflects a specific transcriptional target or general Pol II dysfunction
    • Mechanism linking Rpb9 to left-right asymmetry pathway genes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether the Rpb9-dependent TCR subpathway and Rpb1 degradation mechanism are conserved in mammalian cells, the structural basis of Rpb9's allosteric communication with the trigger loop during the catalytic cycle, and whether Rpb9's roles in autophagy and piRNA biogenesis represent holoenzyme functions or separable moonlighting activities.
  • No mammalian TCR subpathway dissection analogous to yeast Rpb9/Rad26 system
  • No cryo-EM or crystallographic visualization of Rpb9-α21-trigger loop dynamics during catalysis
  • Holoenzyme vs. free Rpb9 contribution to autophagy and piRNA pathways not distinguished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0005198 structural molecule activity 2
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-73894 DNA Repair 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 1 R-HSA-9612973 Autophagy 1
Partners
GCN4RAD26RPB1RPB5TFIIBTFIIETFIIFTFIIS
Complex memberships
RNA polymerase II

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 RPB9 (yeast ortholog of POLR2I) encodes a 122-amino acid, 14.2 kDa subunit of RNA polymerase II that is not essential for mRNA synthesis but is required for normal cell growth over a wide temperature range (heat- and cold-sensitive when deleted). The RPB9 sequence predicted similarity to a Drosophila protein adjacent to the suppressor of Hairy Wing gene. Gene deletion, temperature-sensitivity growth assays, gene sequencing The Journal of biological chemistry High 1918023
1995 RPB9 is required for accurate transcription start site selection by RNA polymerase II. Deletion of RPB9 causes upstream shifts in transcription initiation at multiple promoters both in vitro and in vivo. Reconstitution with recombinant wild-type RPB9 fully corrects the start site defect in vitro, while a mutant RPB9 with an altered metal-binding domain is at least 10-fold less effective. The other 11 Pol II subunits assemble normally in the absence of RPB9. In vitro transcription reconstitution, in vivo promoter analysis, immunoprecipitation of Pol II complex, site-directed mutagenesis of recombinant RPB9 Genes & development High 7883169
1996 RPB9 (SSU73) functionally interacts with the general transcription factor TFIIB. A truncation allele of RPB9 (ssu73-1, lacking the C-terminal 16 amino acids) suppresses both the cold-sensitive growth defect and the downstream shift in transcription start site conferred by the TFIIB mutant sua7-1, establishing a genetic interaction between Rpb9 and TFIIB in start site selection. The C-terminus of Rpb9 functions in start site selection. Genetic suppressor screen, allele sequencing, in vivo transcription start site mapping Nucleic acids research High 8692696
1997 RPB9 regulates transcription elongation through DNA arrest sites in a multistep process with TFIIS. RNA polymerase II lacking RPB9 (pol IIDelta9) elongates more efficiently through pause/arrest sequences but arrested pol IIDelta9 complexes are refractory to TFIIS-stimulated read-through at levels sufficient for wild-type pol II. Addition of purified recombinant RPB9 to pol IIDelta9 restores wild-type elongation properties. Both TFIIS-stimulated transcript cleavage and read-through can be uncoupled. In vitro transcription elongation assays with purified pol IIDelta9, reconstitution with recombinant RPB9, TFIIS titration The Journal of biological chemistry High 9169440
1998 The fission yeast Schizosaccharomyces pombe Rpb9 (113 amino acids, 13,175 Da) is confirmed as a subunit of purified RNA polymerase II by Western blot analysis. S. pombe Rpb9 shares 47%, 40%, and 36% amino acid identity with S. cerevisiae, human, and Drosophila orthologs respectively, establishing conservation of this subunit across eukaryotes. Protein purification, Western blot with anti-Rpb9 antibodies, gene cloning and cDNA sequencing Gene Medium 9852944
2000 The crystal structure of a 10-subunit yeast RNA polymerase II at 3 Å resolution reveals that Rpb9, together with Rpb1 and Rpb5, forms a pair of 'jaws' that grip downstream DNA near the active center. This structural role positions Rpb9 at the periphery of the enzyme, consistent with its regulatory functions in elongation and start site selection. X-ray crystallography at 3 Å resolution Science (New York, N.Y.) High 10784442
2000 RPB9 regulates transcription elongation in vivo. Disruption of RPB9 confers sensitivity to 6-azauracil (a marker of elongation defects) and synthetic phenotypes with the TFIIS gene. The N-terminal zinc ribbon of Rpb9 restores accurate initiation start sites, but the C-terminal zinc ribbon acidic loop (connecting beta-strands 2 and 3) is essential for elongation activity. The conserved linker region (residues 89-95) mediates interaction with RNA polymerase II. Overexpression of TFIIS partially suppresses the 6-azauracil sensitivity of rpb9-deleted cells. In vivo 6-azauracil sensitivity assays, mutagenesis of 20 RPB9 variants, in vitro transcription reconstitution, genome-wide expression profiling The Journal of biological chemistry High 10644677 10938084
2002 Rpb9 mediates a distinct subpathway of transcription-coupled DNA repair (TCR) that is independent of Rad26 (the CSB homolog). The Rpb9 subpathway is more effective in the coding region than upstream of the transcription start site, while the Rad26 subpathway operates equally in both regions. Simultaneous deletion of RPB9 and RAD26 completely abolishes TCR in both regions, showing no other TCR subpathway exists for Pol II-transcribed genes. Rpb4 suppresses the Rpb9 subpathway and facilitates the Rad26 subpathway. UV-induced DNA damage repair mapping, genetic deletion analysis (single and double mutants), strand-specific repair assays The EMBO journal High 12411509
2002 Rpb9 physically interacts with Tfa1, the largest subunit of transcription factor TFIIE, as shown by two-hybrid assay. The interacting fragment of Tfa1 (amino acids 62-164) belongs to a conserved zinc motif. Tfa1/TFIIE co-purifies with RNA polymerase II, and this co-purification is strongly reduced in rpb9-deleted cells, indicating that Rpb9 contributes to recruitment of TFIIE onto RNA polymerase II. Rpb9 mutants are synthetically lethal with loss of the histone acetyltransferase activities of Elongator and SAGA complexes. The critical functional core of Rpb9 is limited to its N-terminal half (first 57 amino acids) that contacts Rpb2 lobe and forms a beta-addition motif with the Rpb1 jaw. Two-hybrid assay, co-immunoprecipitation/co-purification, genetic synthetic lethality analysis, domain deletion analysis The Journal of biological chemistry High 11779853
2003 RNA polymerase II lacking Rpb9 (DeltaRpb9 RNAPII) exhibits an impaired interaction with TFIIF (the Tfg1-Tfg2 complex). In reconstituted transcription assays with highly purified general transcription factors, DeltaRpb9 RNAPII confers upstream shifts in mRNA 5'-end positions, and gel mobility shift assays demonstrate that this is associated with defective Pol II-TFIIF interaction. Thus Rpb9 is required for proper Pol II-TFIIF interaction, which underlies normal start site selection. In vitro reconstituted transcription with purified recombinant TFIIF, gel mobility shift assays, purified DeltaRpb9 polymerase The Journal of biological chemistry High 14522989
2006 Rpb9 plays an important role in transcriptional fidelity in vivo. Deletion of RPB9 causes error-prone transcription as measured by a canavanine-sensitivity assay reading transcription errors in can1-100 mRNA. rpb9-deleted strains show increased transcriptional substitutions and insertions confirmed by cDNA sequencing. Elevated steady-state can1-100 mRNA levels indicate that transcriptional errors reduce sensitivity to nonsense-mediated decay. In contrast, deletion of TFIIS (DST1) had only small effects on fidelity. In vivo transcriptional fidelity assay (canavanine sensitivity), cDNA sequencing of transcription error products, mRNA quantification Proceedings of the National Academy of Sciences of the United States of America High 16492753
2006 The transcription elongation function of Rpb9 is mechanistically linked to its role in TCR. Domain analysis shows that the Zn1 and linker domains are essential for both transcription elongation and TCR functions, while the Zn2 domain is dispensable for both. Impairment of transcription elongation completely abolishes Rpb9-mediated TCR, whereas it does not dramatically compromise Rad26-mediated TCR. Rpb9 becomes dispensable for TCR when its elongation function is compensated for by removing a transcription repression/elongation factor. Domain deletion mutagenesis, UV repair assays, genetic epistasis with elongation factor mutants Molecular and cellular biology High 17030604
2006 Rad26- and Rpb9-mediated TCR subpathways are differentially regulated by promoter elements in the GAL1 gene. Rpb9-mediated repair is strictly transcription-coupled and requires both UAS and TATA sequences; its efficiency depends on the SAGA complex. Rad26-mediated repair initiation is determined by the UAS but not TATA sequences, and can occur in a transcription-independent manner when transcription is too low. UV-induced DNA damage repair mapping in promoter mutants, genetic analysis of SAGA complex mutants, strand-specific repair assays The Journal of biological chemistry Medium 17023424
2007 Rpb9 promotes ubiquitylation and degradation of Rpb1 (the largest Pol II subunit) in response to UV radiation, a function distinct from its TCR and elongation roles. The Zn2 domain of Rpb9, dispensable for elongation/TCR, is essential for promoting Rpb1 degradation. The Zn1 and linker domains play a subsidiary role. Co-immunoprecipitation shows that the full-length Rpb9 is required for strong interaction with core Pol II; deletion of Zn2 dramatically weakens this interaction. Rpb1 itself (not the whole Pol II complex) is degraded via the 26S proteasome. UV irradiation, Western blot for Rpb1 ubiquitylation and degradation, domain deletion mutagenesis, co-immunoprecipitation, proteasome inhibitor studies Molecular and cellular biology High 17452455
2009 Rpb9 controls transcription fidelity by delaying NTP sequestration in the Pol II active center. Deletion of RPB9 substantially enhances NTP misincorporation and increases mismatch extension rates in vitro, similar to the low-fidelity rpb1-E1103G trigger loop mutation. Pre-steady state kinetic analysis shows RPB9 deletion promotes premature NTP sequestration just prior to phosphodiester bond formation. Rpb9 modulates fidelity via interaction between its C-terminal domain and the trigger loop (a mobile catalytic element of Rpb1), despite being located at a distance from the active center. Pre-steady state kinetic analysis of NTP incorporation, in vitro misincorporation assays, genetic synthetic lethality with trigger loop mutant The Journal of biological chemistry High 19439405
2013 Rpb9 functions in transcriptional proofreading by two mechanisms: (1) it reduces the rate of error propagation (extension of mismatched RNA 3' end) by 2- to 3-fold across multiple sequence contexts; (2) it facilitates TFIIS-mediated error excision by promoting formation of the RNA cleavage-competent conformation. In the absence of Rpb9, both error propagation rate increases and TFIIS-mediated excision is compromised. Rpb9 does not affect NTP selectivity (initial nucleotide discrimination). In vitro transcription elongation fidelity assays with defined mismatched complexes, TFIIS cleavage assays, kinetic analysis Biochemistry High 24099331
2016 Rpb9 indirectly affects trigger loop (TL) mobility in RNA polymerase II rather than directly contacting the TL. The mushroom toxin α-amanitin (which inhibits TL mobility) suppresses the effect of RPB9 deletion on NTP misincorporation, linking Rpb9 function to TL. Missense alleles of RPB9 suppress the growth defect of rpb1-G730D (substitution in Rpb1 α-helix 21, which directly contacts the TL during opening/closing). Rpb9 anchors the position of α21 to modulate TL function; Rpb9 or α21 substitutions disrupting this interaction phenocopy rpb9Δ. Epistasis analysis shows rpb9Δ combined with fast rpb1 alleles does not increase misincorporation beyond rpb9Δ alone, confirming shared mechanism. α-amanitin inhibition assay, genetic suppressor identification, in vitro elongation rate and misincorporation assays, epistasis analysis The Journal of biological chemistry High 27226557
2018 In rpb9-deleted yeast cells, simultaneous mutation of multiple N-terminal lysines in histone H3 is lethal. Rpb9 deficiency leads to suppressed activation of DNA damage checkpoint regulators γH2A and Rad53 in response to DNA damage, and histone H3 hypoacetylation causes inefficient repair of DNA double-strand breaks. Loss of both Rpb9 and H3 acetylation leads to genomic instability and aberrant chromosome segregation in mitosis. Genetic interaction (synthetic lethality), flow cytometry, immunoblot for checkpoint markers (γH2A, Rad53), microscopy of chromosome segregation Scientific reports Medium 29440683
2021 In C. elegans, RPB-9 (POLR2I ortholog) is required for piRNA-mediated gene silencing and piRNA biogenesis. RPB-9 recruits the Integrator complex to piRNA genes to promote transcriptional termination. Genetic and biochemical evidence shows RPB-9 is needed to initiate heritable piRNA-mediated silencing at DNA transposon families and somatic genes in the germline. Genetic (rpb-9 mutant analysis), co-immunoprecipitation/biochemical evidence for Integrator complex recruitment, piRNA sequencing, reporter silencing assays The EMBO journal High 33533030
2022 The RNA polymerase II subunit Rpb9 activates ATG1 transcription to promote autophagy. Rpb9 binds to the ATG1 promoter region, an interaction mediated by the transcription factor Gcn4. Rpb9 deficiency decreases autophagic activity. This function is conserved in mammalian cells, where POLR2I regulates ULK1 (the ATG1 homolog) transcription. Identified through a genome-wide screen of S. cerevisiae knockout library. High-throughput knockout screen, chromatin immunoprecipitation (ChIP) at ATG1 promoter, autophagy flux assays, mammalian cell knockdown with ULK1 mRNA/autophagy readouts EMBO reports High 36102592
2025 Knockdown of polr2i in zebrafish (morpholino-mediated) causes severe cardiac malformations including elongated heart tubes with reduced chamber overlap, pericardial edema, decreased ejection fraction, cardiac output, and volume per beat. Angiogenesis is also disrupted (reduced intersegmental vessels and caudal vein plexus). Mitochondrial quality in myocardial cells is impaired, and left-right asymmetry of heart, liver, and pancreas is defective. Rescue with capped polr2i mRNA confirmed phenotype specificity. POLR2I protein sequence exceeds 90% similarity across vertebrates. Morpholino knockdown in zebrafish, mRNA rescue experiments, transgenic fluorescent reporter lines, cardiac function measurement (ejection fraction, cardiac output), o-Dianisidine staining, qRT-PCR of cardiovascular markers Frontiers in bioscience (Landmark edition) Medium 41198546

Source papers

Stage 0 corpus · 55 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
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
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
2008 Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 787 18854154
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
2000 Architecture of RNA polymerase II and implications for the transcription mechanism. Science (New York, N.Y.) 452 10784442
2011 HIV latency. Cold Spring Harbor perspectives in medicine 439 22229121
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
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
2009 The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes & development 285 19240132
2011 Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 281 21729782
2004 The DNA sequence and biology of human chromosome 19. Nature 271 15057824
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
2002 Rpb4 and Rpb9 mediate subpathways of transcription-coupled DNA repair in Saccharomyces cerevisiae. The EMBO journal 109 12411509
1997 Transcription elongation through DNA arrest sites. A multistep process involving both RNA polymerase II subunit RPB9 and TFIIS. The Journal of biological chemistry 101 9169440
1995 RNA polymerase II subunit RPB9 is required for accurate start site selection. Genes & development 96 7883169
1991 Yeast RNA polymerase II subunit RPB9 is essential for growth at temperature extremes. The Journal of biological chemistry 86 1918023
2000 RNA polymerase II subunit Rpb9 regulates transcription elongation in vivo. The Journal of biological chemistry 81 10938084
2009 Rpb9 subunit controls transcription fidelity by delaying NTP sequestration in RNA polymerase II. The Journal of biological chemistry 72 19439405
2006 RNA polymerase II subunit Rpb9 is important for transcriptional fidelity in vivo. Proceedings of the National Academy of Sciences of the United States of America 69 16492753
1996 Functional interaction between TFIIB and the Rpb9 (Ssu73) subunit of RNA polymerase II in Saccharomyces cerevisiae. Nucleic acids research 55 8692696
2002 The Rpb9 subunit of RNA polymerase II binds transcription factor TFIIE and interferes with the SAGA and elongator histone acetyltransferases. The Journal of biological chemistry 51 11779853
2011 Point mutations in the Rpb9-homologous domain of Rpc11 that impair transcription termination by RNA polymerase III. Nucleic acids research 32 21450810
2007 Yeast Rpb9 plays an important role in ubiquitylation and degradation of Rpb1 in response to UV-induced DNA damage. Molecular and cellular biology 30 17452455
2000 Yeast RNA polymerase II subunit RPB9. Mapping of domains required for transcription elongation. The Journal of biological chemistry 29 10644677
2013 Fidelity of RNA polymerase II transcription: Role of Rpb9 [corrected] in error detection and proofreading. Biochemistry 25 24099331
2021 The RNA polymerase II subunit RPB-9 recruits the integrator complex to terminate Caenorhabditis elegans piRNA transcription. The EMBO journal 24 33533030
2006 Evidence that the transcription elongation function of Rpb9 is involved in transcription-coupled DNA repair in Saccharomyces cerevisiae. Molecular and cellular biology 24 17030604
2003 Yeast RNA polymerase II lacking the Rpb9 subunit is impaired for interaction with transcription factor IIF. The Journal of biological chemistry 24 14522989
1998 Identification of the gene and the protein of RNA polymerase II subunit 9 (Rpb9) from the fission yeast Schizosacharomyces pombe. Gene 17 9852944
2016 RNA Polymerase II Trigger Loop Mobility: INDIRECT EFFECTS OF Rpb9. The Journal of biological chemistry 16 27226557
2006 Modulation of Rad26- and Rpb9-mediated DNA repair by different promoter elements. The Journal of biological chemistry 11 17023424
2018 Rpb9-deficient cells are defective in DNA damage response and require histone H3 acetylation for survival. Scientific reports 9 29440683
2022 The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy. EMBO reports 5 36102592
2021 Deletion of the non-essential Rpb9 subunit of RNA polymerase II results in pleiotropic phenotypes in Schizosaccharomyces pombe. Biochimica et biophysica acta. Proteins and proteomics 3 33775921
2022 Absence of the Rpb9 subunit of RNA polymerase II reduces the chronological life span in fission yeast. Journal of basic microbiology 2 35618649
2025 polr2i is Required for Zebrafish Early Cardiac Development. Frontiers in bioscience (Landmark edition) 0 41198546
2000 [Chromosomal localization of rpb9+ and tfa1+ genes, coding for components of the mRNA synthesis apparatus of Schizosaccharomyces pombe]. Bioorganicheskaia khimiia 0 11041002