id: MODULE:rna_polymerase_iii_transcription title: Human RNA polymerase III transcription — type 1 (TFIIIA-TFIIIC), type 2 (TFIIIC) and type 3 (SNAPc) promoter recognition, BRF1- or BRF2-TFIIIB recruitment, the 17-subunit Pol III with RPC7 paralogue choice, intrinsic termination, and MAF1 repression description: >- RNA polymerase III (Pol III) transcribes short, abundant non-coding RNAs: all tRNAs, 5S rRNA, U6 snRNA, 7SK RNA, the RNA components of RNase P and RNase MRP, 7SL RNA, vault and Y RNAs. It is recruited by the TFIIIB complex, which in turn is placed upstream of the start site by promoter-specific assembly factors. Three promoter types differ in how this happens. Type 1 promoters (5S rRNA genes) have an internal control region bound by the zinc-finger factor TFIIIA, which recruits the six-subunit TFIIIC. Type 2 promoters (tRNA genes and others) have internal A and B boxes bound directly by TFIIIC. Type 3 promoters (U6, 7SK and other gene-external promoters, found in vertebrates) have an upstream proximal sequence element bound by the five-subunit snRNA-activating protein complex SNAPc and a TATA box. TFIIIB consists of the TATA-box binding protein TBP, the SANT-domain protein BDP1 and a TFIIB-related factor, BRF1 at type 1 and type 2 promoters or BRF2 at type 3 promoters. Pol III has 17 subunits: the catalytic RPC1 (POLR3A) and RPC2 (POLR3B), the RPAC1 and RPAC2 subunits shared with Pol I (POLR1C, POLR1D), the five RPABC subunits shared with Pol I and Pol II (POLR2E, POLR2F, POLR2H, POLR2K, POLR2L), the TFIIE-like heterotrimer RPC3-RPC6-RPC7 (POLR3C, POLR3F, and POLR3G or its paralogue POLR3GL), the TFIIF-like heterodimer RPC4-RPC5 (POLR3D, POLR3E), the RPC8-RPC9 stalk (POLR3H, CRCP) and the TFIIS-like RPC10 (POLR3K). Pol III terminates without accessory factors at a run of thymidines on the non-template strand and re-initiates efficiently on the same gene. Under nutrient limitation or stress, the dephosphorylated repressor MAF1 binds Pol III and prevents its recruitment by TFIIIB. status: DRAFT scope: CONCRETE evidence: - source_id: PW:0000128 title: RNA polymerase III transcription pathway statement: >- The module boundary follows the RGD Pathway Ontology term and its diagram, which draws TFIIIA with TFIIIC, TFIIIC with TFIIIB, SNAPc with TFIIIB (with Pou2f1 and Zfp143 acting on SNAPc), TFIIIB with RNA polymerase III, RNA polymerase III producing the pre-tRNA transcript, Maf1 and Rb1 inhibiting TFIIIB and Pol III or SNAPc, and Sub1 with TFIIIB and TFIIIC. Derived through projects/RGD_PATHWAY_ONTOLOGY (pathways/PW_0000128.yaml). - source_id: GO:0006383 title: transcription by RNA polymerase III statement: >- The GO process mapped to PW:0000128 (skos:relatedMatch, from the PW definition cross-reference in projects/RGD_PATHWAY_ONTOLOGY/data/module_seeds.yaml). It is the module's process concept. - source_id: PMID:18644873 title: Different functional modes of p300 in activation of RNA polymerase III transcription from chromatin templates. statement: Pol III needs TFIIIB and TFIIIC, plus TFIIIA at 5S genes; TFIIIC reads the A and B boxes of type 2 genes and directs TFIIIB and Pol III binding. supporting_text: In the case of tRNA and VA1 genes (subclass 2 genes), gene-internal core promoter elements (A and B boxes) are recognized directly by TFIIIC, which in turn directs the sequential binding of TFIIIB and Pol III. - source_id: PMID:28743884 title: Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation. statement: TFIIIB is TBP, BDP1 and BRF1 or BRF2; BRF2 replaces BRF1 at type 3 promoters, which carry a TATA box and an upstream PSE bound by SNAPc. supporting_text: In vertebrates, the TFIIB-related factor II (Brf2) replaces Brf1 at type III promoters such as the U6 snRNA promoter, which, unlike the other types of Pol III promoters, are characterized by the presence of a strong TATA box and an upstream proximal sequence (PSE) recognized by the multisubunit transcription factor SNAPc notes: >- Derived from the RGD Pathway Ontology diagram PW:0000128 (RNA polymerase III transcription pathway) through the RGD_PATHWAY_ONTOLOGY project's diagram->module route (seed in projects/RGD_PATHWAY_ONTOLOGY/data/module_seeds.yaml, tier related_module_only because the mapped GO term is shared with the fly module). RGD curates 58 human genes to PW:0000128: BDP1 BRF1 BRF2 CLP1 CRCP ELAC1 ELAC2 GTF3A GTF3C1 GTF3C2 GTF3C3 GTF3C4 GTF3C5 GTF3C6 MAF1 POLR1C POLR1D POLR2E POLR2F POLR2H POLR2K POLR2L POLR3A POLR3B POLR3C POLR3D POLR3E POLR3F POLR3G POLR3GL POLR3H POLR3K POP1 POP4 POP5 POP7 POU2F1 RB1 RPP14 RPP21 RPP25 RPP30 RPP38 RPP40 RTCB SNAPC1 SNAPC2 SNAPC3 SNAPC4 SNAPC5 SSB SUB1 TBP TSEN15 TSEN2 TSEN34 TSEN54 ZNF143. Thirty-six are modelled as participants: GTF3A; the six TFIIIC subunits; the five SNAPc subunits; TBP, BRF1, BRF2 and BDP1; the 17 Pol III subunit genes plus the RPC7 paralogue POLR3GL (18 genes for 17 positions); and MAF1. No gene outside the RGD list is added. Molecular functions were taken from each protein's experimental GO annotations in QuickGO (November 2026); none of the participants has a gene review in this repository. Two functions are curator-authored without an experimental human GOA row: TFIIIA RNA polymerase III type 1 promoter sequence-specific DNA binding (the GO definition of that term names TFIIIA as the type 1 recognition factor) and MAF1 RNA polymerase inhibitor activity (reasons in the annoton). UniProt labels are the current recommended names (UniProt REST, November 2026). Boundary decisions. (1) Promoter types as a ROUTE variant set. The three types use different assembly factors (TFIIIA then TFIIIC; TFIIIC alone; SNAPc) to reach the same intermediate, TFIIIB bound upstream of the start site, so they are three variants of part 1 (selection ONE_OR_MORE: each gene uses one type and every cell uses all three). TFIIIC is therefore written twice, as separate annotons in the type 1 and type 2 variants with the same six subunits, because annoton ids must be unique and a variant cannot reference a sibling. (2) TFIIIB as a REALIZER variant set. Both forms carry the same activity; BRF1-TFIIIB serves type 1 and type 2 promoters and BRF2-TFIIIB serves type 3 promoters. The pairing of a promoter type with a TFIIIB form is stated in the labels and descriptions; it is not encoded as a constraint because the variant sets are independent. TBP and BDP1 are listed in both forms. (3) The enzyme is one complex annoton with 17 active units, matching modules/dmel_nuclear_rna_polymerases.yaml (the Drosophila counterpart) and the Pol I module. The RPC7 position is a FAMILY unit with POLR3G and POLR3GL as representative members, which records the paralogue choice without writing the 17-subunit enzyme out twice. No PANTHER id is asserted for it (the validator's informational notice about this is expected). Units without a function are those whose experimental GOA rows are limited to chromatin binding (POLR3D, POLR3G), zinc binding (POLR3K, POLR2L) or a complex-level polymerase activity assigned to a small subunit (POLR3H, CRCP). (4) Shared subunits. The five RPABC subunits (POLR2E, POLR2F, POLR2H, POLR2K, POLR2L) and the two RPAC subunits (POLR1C, POLR1D, the latter as P0DPB6) are listed in both this module and modules/rna_polymerase_i_transcription.yaml with the same accessions and roles. No human RNA polymerase II module exists, and none is created here. (5) Elongation, termination and reinitiation are intrinsic to Pol III and are concepts of the enzyme node. SUB1 (PC4), which RGD draws with TFIIIB and TFIIIC as a reinitiation and termination factor, is excluded: its experimental functions in GOA are DNA binding and RNA polymerase II coactivator activity, and its Pol III role is stimulatory rather than a step the basal system cannot perform. (6) MAF1 is an optional regulatory part connected to the enzyme by NEGATIVELY_REGULATES; its upstream control by mTORC1 (PW:0000180) is named, not modelled. RB1, which RGD draws inhibiting TFIIIB and SNAPc, is excluded as a pleiotropic repressor whose main role is outside Pol III transcription (it has its own gene review). (7) POU2F1 (Oct-1) and ZNF143 (Staf), which bind the distal sequence element of type 3 promoters and stimulate SNAPc binding, are excluded as gene-specific activators shared with Pol II snRNA promoters; they are not required for basal type 3 transcription. (8) tRNA processing is out of scope: RNase P (POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38, RPP40), RNase Z (ELAC1, ELAC2), tRNA splicing (TSEN2, TSEN15, TSEN34, TSEN54, CLP1, RTCB) and the La protein SSB act on the transcript after synthesis and belong to the tRNA maturation pathway (PW:0001573). The chromatin modification/remodeling link (PW:0001337) is also out of scope. (9) Pol III's separate role as a cytosolic DNA sensor that transcribes AT-rich DNA into immunostimulatory RNA is not modelled; the module is limited to nuclear transcription of Pol III genes. (10) Substrate versus participant: the DNA template and the RNA products are not participants. GO-CAM links. No production GO-CAM model in gocams/index.tsv contains any Pol III subunit, TFIIIA, TFIIIB, TFIIIC, SNAPc or MAF1; TBP appears only in two Pol II models (ZNF76 regulation of TBP), which are not linked. The seed's best_gocam, gomodel:63f809ec00000701 (tRNA repair and recycling by ANKZF1, ELAC1 and TRNT1), overlaps only through ELAC1, a tRNA-processing enzyme excluded here, so no gocam_associations are recorded. PANTHER family ids and PTNs are deliberately not asserted. module: id: rna_polymerase_iii_transcription label: Human RNA polymerase III transcription module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: transcription by RNA polymerase III term: id: GO:0006383 label: transcription by RNA polymerase III description: The GO process mapped to PW:0000128. context: taxa: - preferred_term: Homo sapiens term: id: NCBITaxon:9606 label: Homo sapiens cellular_components: - preferred_term: nucleoplasm term: id: GO:0005654 label: nucleoplasm parts: - order: 1 role: promoter recognition by a promoter-type-specific assembly factor node: id: promoter_recognition label: Pol III promoter recognition (type 1, type 2 or type 3) module_type: BIOLOGICAL_PROCESS description: >- The three promoter types use different DNA-binding assembly factors to place TFIIIB upstream of the start site. Each gene uses one type; a cell uses all three. concepts: - preferred_term: RNA polymerase III preinitiation complex assembly term: id: GO:0070898 label: RNA polymerase III preinitiation complex assembly variant_sets: - id: pol3_promoter_type label: Pol III promoter type axis: promoter architecture of the transcribed gene (internal control region, internal A and B boxes, or upstream PSE and TATA box) variant_kind: ROUTE selection: ONE_OR_MORE variants: - id: type1_promoter label: Type 1 promoter (5S rRNA genes) read by TFIIIA, which recruits TFIIIC module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: 5S class rRNA transcription by RNA polymerase III term: id: GO:0042791 label: 5S class rRNA transcription by RNA polymerase III annotons: - id: tfiiia_icr_binding label: TFIIIA binds the internal control region of the 5S rRNA gene participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3A term: id: UniProtKB:Q92664 label: Transcription factor IIIA function: preferred_term: RNA polymerase III type 1 promoter sequence-specific DNA binding term: id: GO:0001002 label: RNA polymerase III type 1 promoter sequence-specific DNA binding processes: - preferred_term: 5S class rRNA transcription by RNA polymerase III term: id: GO:0042791 label: 5S class rRNA transcription by RNA polymerase III role_description: >- Nine-zinc-finger factor that binds the internal control region of the 5S rRNA gene (and the 5S rRNA itself). The molecular function is curator-authored from the GO definition of the type 1 promoter term, which names TFIIIA as the recognition factor; human GTF3A's only experimental molecular-function row in GOA is 5S rRNA binding (IDA), its post-transcriptional role. evidence: - source_id: PMID:18644873 statement: TFIIIA is the 5S gene-specific Pol III transcription factor. supporting_text: Accurate and specific transcription of DNA templates by Pol III requires the assistance of the general initiation transcription factors TFIIIB and TFIIIC and, in some cases, various gene-specific factors such as the 5S gene-specific factor TFIIIA - id: tfiiic_type1 label: TFIIIC assembles on TFIIIA-bound 5S rRNA genes participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: TFIIIC (GTF3C1-6) term: id: GO:0000127 label: transcription factor TFIIIC complex active_units: - id: t1_gtf3c1 label: GTF3C1 role: TFIIIC220, tau-B subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C1 term: id: UniProtKB:Q12789 label: General transcription factor 3C polypeptide 1 - id: t1_gtf3c2 label: GTF3C2 role: TFIIIC110, tau-B subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C2 term: id: UniProtKB:Q8WUA4 label: General transcription factor 3C polypeptide 2 - id: t1_gtf3c3 label: GTF3C3 role: TFIIIC102, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C3 term: id: UniProtKB:Q9Y5Q9 label: General transcription factor 3C polypeptide 3 - id: t1_gtf3c4 label: GTF3C4 role: TFIIIC90, tau-B subunit; has histone acetyltransferase activity. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C4 term: id: UniProtKB:Q9UKN8 label: General transcription factor 3C polypeptide 4 - id: t1_gtf3c5 label: GTF3C5 role: TFIIIC63, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C5 term: id: UniProtKB:Q9Y5Q8 label: General transcription factor 3C polypeptide 5 - id: t1_gtf3c6 label: GTF3C6 role: TFIIIC35, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C6 term: id: UniProtKB:Q969F1 label: General transcription factor 3C polypeptide 6 function: preferred_term: RNA polymerase III general transcription initiation factor activity term: id: GO:0000995 label: RNA polymerase III general transcription initiation factor activity processes: - preferred_term: 5S class rRNA transcription by RNA polymerase III term: id: GO:0042791 label: 5S class rRNA transcription by RNA polymerase III role_description: >- Same complex as the type 2 annoton, repeated here because TFIIIC is recruited by TFIIIA rather than by DNA at type 1 promoters. connections: - source: tfiiia_icr_binding target: tfiiic_type1 connection_type: PRECEDES description: DNA-bound TFIIIA recruits TFIIIC. - id: type2_promoter label: Type 2 promoter (tRNA and related genes) read directly by TFIIIC at the A and B boxes module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: tRNA transcription by RNA polymerase III term: id: GO:0042797 label: tRNA transcription by RNA polymerase III annotons: - id: tfiiic_type2 label: TFIIIC binds the internal A and B boxes participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: TFIIIC (GTF3C1-6) term: id: GO:0000127 label: transcription factor TFIIIC complex active_units: - id: t2_gtf3c1 label: GTF3C1 role: TFIIIC220, tau-B subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C1 term: id: UniProtKB:Q12789 label: General transcription factor 3C polypeptide 1 - id: t2_gtf3c2 label: GTF3C2 role: TFIIIC110, tau-B subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C2 term: id: UniProtKB:Q8WUA4 label: General transcription factor 3C polypeptide 2 - id: t2_gtf3c3 label: GTF3C3 role: TFIIIC102, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C3 term: id: UniProtKB:Q9Y5Q9 label: General transcription factor 3C polypeptide 3 - id: t2_gtf3c4 label: GTF3C4 role: TFIIIC90, tau-B subunit; has histone acetyltransferase activity. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C4 term: id: UniProtKB:Q9UKN8 label: General transcription factor 3C polypeptide 4 - id: t2_gtf3c5 label: GTF3C5 role: TFIIIC63, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C5 term: id: UniProtKB:Q9Y5Q8 label: General transcription factor 3C polypeptide 5 - id: t2_gtf3c6 label: GTF3C6 role: TFIIIC35, tau-A subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: GTF3C6 term: id: UniProtKB:Q969F1 label: General transcription factor 3C polypeptide 6 function: preferred_term: RNA polymerase III general transcription initiation factor activity term: id: GO:0000995 label: RNA polymerase III general transcription initiation factor activity processes: - preferred_term: tRNA transcription by RNA polymerase III term: id: GO:0042797 label: tRNA transcription by RNA polymerase III role_description: >- The six subunits form the tau-B (GTF3C1, GTF3C2, GTF3C4) and tau-A (GTF3C3, GTF3C5, GTF3C6) lobes that contact the B and A boxes. The complex function is the IDA row shared by all six subunits (PMID:17409385); GTF3C4 also has histone acetyltransferase rows, which are not modelled. evidence: - source_id: PMID:17409385 statement: Human TFIIIC has six subunits and is required for tRNA and 5S RNA gene transcription. supporting_text: TFIIIC in yeast and humans is required for transcription of tRNA and 5 S RNA genes by RNA polymerase III. - source_id: PMID:18644873 statement: The six-subunit TFIIIC2 binds the B box directly. supporting_text: TFIIIC2 is a stable complex of six subunits (220, 110, 102, 90, 63, and 35 kDa) that binds directly to the B box - id: type3_promoter label: Type 3 promoter (U6, 7SK and related genes) read by SNAPc at the PSE module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: snRNA transcription by RNA polymerase III term: id: GO:0042796 label: snRNA transcription by RNA polymerase III annotons: - id: snapc_pse_binding label: SNAPc binds the proximal sequence element participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: SNAPc (SNAPC1-5) term: id: GO:0019185 label: snRNA-activating protein complex active_units: - id: snapc_snapc1 label: SNAPC1 role: SNAP43. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SNAPC1 term: id: UniProtKB:Q16533 label: snRNA-activating protein complex subunit 1 - id: snapc_snapc2 label: SNAPC2 role: SNAP45. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SNAPC2 term: id: UniProtKB:Q13487 label: snRNA-activating protein complex subunit 2 - id: snapc_snapc3 label: SNAPC3 role: SNAP50. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SNAPC3 term: id: UniProtKB:Q92966 label: snRNA-activating protein complex subunit 3 - id: snapc_snapc4 label: SNAPC4 role: SNAP190, Myb-domain subunit that contacts the PSE and binds Oct-1. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SNAPC4 term: id: UniProtKB:Q5SXM2 label: snRNA-activating protein complex subunit 4 - id: snapc_snapc5 label: SNAPC5 role: SNAP19. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SNAPC5 term: id: UniProtKB:O75971 label: snRNA-activating protein complex subunit 5 function: preferred_term: RNA polymerase III general transcription initiation factor activity term: id: GO:0000995 label: RNA polymerase III general transcription initiation factor activity processes: - preferred_term: snRNA transcription by RNA polymerase III term: id: GO:0042796 label: snRNA transcription by RNA polymerase III role_description: >- SNAPc also acts at the PSE of Pol II snRNA promoters; only its Pol III role is modelled. The function is the IDA row of SNAPC4 and SNAPC5 (PMID:9418884, PMID:9732265). evidence: - source_id: PMID:9732265 statement: Five recombinant subunits reconstitute a SNAPc that binds the PSE and directs Pol II and Pol III snRNA transcription. supporting_text: This recombinant complex binds specifically to the PSE and directs both RNA polymerase II and III snRNA gene transcription. - source_id: PMID:9418884 statement: SNAP190 contributes the Myb domain that recognises the PSE. supporting_text: the largest subunit of the SNAP complex is involved in direct recognition of the PSE and is a target for the Oct-1 activator - order: 2 role: TFIIIB recruitment upstream of the start site node: id: tfiiib_recruitment label: TFIIIB (TBP-BDP1 with BRF1 or BRF2) is placed upstream of the start site module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: transcription initiation at RNA polymerase III promoter term: id: GO:0006384 label: transcription initiation at RNA polymerase III promoter variant_sets: - id: tfiiib_form label: TFIIIB form axis: TFIIB-related subunit (BRF1 at type 1 and 2 promoters, BRF2 at type 3 promoters) variant_kind: REALIZER selection: ONE_OR_MORE variants: - id: tfiiib_brf1_form label: BRF1-TFIIIB (TFIIIB-beta) at type 1 and type 2 promoters module_type: PROTEIN_COMPLEX annotons: - id: tfiiib_brf1 label: TBP-BRF1-BDP1 recruited by TFIIIC participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: TFIIIB-beta (TBP, BRF1, BDP1) term: id: GO:0034733 label: transcription factor TFIIIB-beta complex active_units: - id: tfiiib1_tbp label: TBP role: TATA-box binding protein, shared with SL1 and TFIID. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TBP term: id: UniProtKB:P20226 label: TATA-box-binding protein - id: tfiiib1_brf1 label: BRF1 role: TFIIB-related factor 1; bridges TBP to Pol III at type 1 and type 2 promoters. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: BRF1 term: id: UniProtKB:Q92994 label: Transcription factor IIIB 90 kDa subunit - id: tfiiib1_bdp1 label: BDP1 role: SANT-domain subunit that locks TFIIIB onto DNA. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: BDP1 term: id: UniProtKB:A6H8Y1 label: Transcription factor TFIIIB component B'' homolog function: preferred_term: RNA polymerase III general transcription initiation factor activity term: id: GO:0000995 label: RNA polymerase III general transcription initiation factor activity processes: - preferred_term: transcription initiation at RNA polymerase III promoter term: id: GO:0006384 label: transcription initiation at RNA polymerase III promoter role_description: >- TBP carries the IMP row for RNA polymerase III general transcription initiation factor activity (PMID:26638071). BRF1 and BDP1 have no experimental molecular-function row in human GOA (their IBA rows are the same initiation factor activity and type 3 promoter binding); they are units without a function. evidence: - source_id: PMID:28743884 statement: TFIIIB is TBP, BRF1 and BDP1; BRF1 and BRF2 bridge Pol III to the promoter. supporting_text: "The TFIIIB complex is composed of three subunits: the TATA-binding protein (TBP), TFIIB-related factor 1 (Brf1)" - id: tfiiib_brf2_form label: BRF2-TFIIIB (TFIIIB-alpha) at type 3 promoters module_type: PROTEIN_COMPLEX annotons: - id: tfiiib_brf2 label: TBP-BRF2-BDP1 binds the TATA box together with SNAPc participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: TFIIIB-alpha (TBP, BRF2, BDP1) term: id: GO:0034732 label: transcription factor TFIIIB-alpha complex active_units: - id: tfiiib2_tbp label: TBP role: TATA-box binding protein; binds the TATA box of type 3 promoters. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TBP term: id: UniProtKB:P20226 label: TATA-box-binding protein - id: tfiiib2_brf2 label: BRF2 role: TFIIB-related factor 2; replaces BRF1 at type 3 promoters. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: BRF2 term: id: UniProtKB:Q9HAW0 label: Transcription factor IIIB 50 kDa subunit function: preferred_term: RNA polymerase III type 3 promoter sequence-specific DNA binding term: id: GO:0001006 label: RNA polymerase III type 3 promoter sequence-specific DNA binding - id: tfiiib2_bdp1 label: BDP1 role: SANT-domain subunit that locks TFIIIB onto DNA. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: BDP1 term: id: UniProtKB:A6H8Y1 label: Transcription factor TFIIIB component B'' homolog function: preferred_term: RNA polymerase III general transcription initiation factor activity term: id: GO:0000995 label: RNA polymerase III general transcription initiation factor activity processes: - preferred_term: snRNA transcription by RNA polymerase III term: id: GO:0042796 label: snRNA transcription by RNA polymerase III role_description: >- BRF2 carries the IDA row for RNA polymerase III type 3 promoter sequence-specific DNA binding and TBP the IMP row for the general initiation factor activity, both from PMID:26638071. evidence: - source_id: PMID:26638071 statement: BRF2-TFIIIB recruits Pol III to type 3 promoters, binding the TATA box together with SNAPc at the PSE. supporting_text: The Brf2-containing TFIIIB complex recruits Pol III to type III promoters, characterized by a TATA box located 20–25 base pairs (bp) upstream of the transcriptional start site and a proximal sequence element (PSE) located further upstream - order: 3 role: transcription, termination and reinitiation node: id: pol3_transcription label: Pol III transcribes and terminates at a thymidine run module_type: PROTEIN_COMPLEX concepts: - preferred_term: transcription elongation by RNA polymerase III term: id: GO:0006385 label: transcription elongation by RNA polymerase III - preferred_term: termination of RNA polymerase III transcription term: id: GO:0006386 label: termination of RNA polymerase III transcription annotons: - id: pol3_enzyme label: RNA polymerase III (17 subunits) participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: RNA polymerase III term: id: GO:0005666 label: RNA polymerase III complex active_units: - id: pol3_polr3a label: POLR3A role: RPC1, largest catalytic subunit; forms the active centre and DNA cleft with RPC2. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3A term: id: UniProtKB:O14802 label: DNA-directed RNA polymerase III subunit RPC1 function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity - id: pol3_polr3b label: POLR3B role: RPC2, second-largest catalytic subunit; forms the active centre with RPC1. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3B term: id: UniProtKB:Q9NW08 label: DNA-directed RNA polymerase III subunit RPC2 function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity - id: pol3_rpac1_polr1c label: POLR1C role: RPAC1 (AC40), shared by Pol I and Pol III; forms the assembly platform with RPAC2 (alpha-like heterodimer). participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR1C term: id: UniProtKB:O15160 label: DNA-directed RNA polymerases I and III subunit RPAC1 - id: pol3_rpac2_polr1d label: POLR1D role: RPAC2 (AC19), shared by Pol I and Pol III; partner of RPAC1. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR1D term: id: UniProtKB:P0DPB6 label: DNA-directed RNA polymerases I and III subunit RPAC2 - id: pol3_rpabc1_polr2e label: POLR2E role: RPABC1, shared by Pol I, II and III; part of the lower jaw and core. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR2E term: id: UniProtKB:P19388 label: DNA-directed RNA polymerases I, II, and III subunit RPABC1 - id: pol3_rpabc2_polr2f label: POLR2F role: RPABC2, shared by Pol I, II and III; associates with the largest subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR2F term: id: UniProtKB:P61218 label: DNA-directed RNA polymerases I, II, and III subunit RPABC2 - id: pol3_rpabc3_polr2h label: POLR2H role: RPABC3, shared by Pol I, II and III. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR2H term: id: UniProtKB:P52434 label: DNA-directed RNA polymerases I, II, and III subunit RPABC3 - id: pol3_rpabc4_polr2k label: POLR2K role: RPABC4, shared by Pol I, II and III; zinc-binding core subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR2K term: id: UniProtKB:P53803 label: DNA-directed RNA polymerases I, II, and III subunit RPABC4 - id: pol3_rpabc5_polr2l label: POLR2L role: RPABC5, shared by Pol I, II and III; zinc-binding core subunit. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR2L term: id: UniProtKB:P62875 label: DNA-directed RNA polymerases I, II, and III subunit RPABC5 - id: pol3_polr3c label: POLR3C role: RPC3 (RPC62), TFIIE-alpha-like subunit of the RPC3-RPC6-RPC7 initiation heterotrimer; binds single-stranded DNA. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3C term: id: UniProtKB:Q9BUI4 label: DNA-directed RNA polymerase III subunit RPC3 function: preferred_term: single-stranded DNA binding term: id: GO:0003697 label: single-stranded DNA binding - id: pol3_polr3f label: POLR3F role: RPC6 (RPC39), heterotrimer subunit that binds duplex DNA; carries a 4Fe-4S cluster. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3F term: id: UniProtKB:Q9H1D9 label: DNA-directed RNA polymerase III subunit RPC6 function: preferred_term: double-stranded DNA binding term: id: GO:0003690 label: double-stranded DNA binding - id: pol3_rpc7 label: RPC7 (POLR3G or POLR3GL) role: RPC7 (RPC32), third subunit of the heterotrimer that tethers it to the stalk; encoded by two paralogues, one of which is incorporated into a given enzyme (RPC7-alpha, POLR3G, enriched in stem and cancer cells; RPC7-beta, POLR3GL, broadly expressed). participant: selector_type: FAMILY family: preferred_term: RPC7 paralogues (POLR3G, POLR3GL) representative_members: - preferred_term: POLR3G term: id: UniProtKB:O15318 label: DNA-directed RNA polymerase III subunit RPC7 - preferred_term: POLR3GL term: id: UniProtKB:Q9BT43 label: DNA-directed RNA polymerase III subunit RPC7-like - id: pol3_polr3d label: POLR3D role: RPC4 (RPC53), with RPC5 the TFIIF-like heterodimer acting in initiation and termination. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3D term: id: UniProtKB:P05423 label: DNA-directed RNA polymerase III subunit RPC4 - id: pol3_polr3e label: POLR3E role: RPC5 (RPC80), partner of RPC4 in the TFIIF-like heterodimer; its vertebrate C-terminal extension aids assembly and stability. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3E term: id: UniProtKB:Q9NVU0 label: DNA-directed RNA polymerase III subunit RPC5 - id: pol3_polr3h label: POLR3H role: RPC8, stalk subunit with RPC9. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3H term: id: UniProtKB:Q9Y535 label: DNA-directed RNA polymerase III subunit RPC8 - id: pol3_crcp label: CRCP role: RPC9 (CGRP-RCP), stalk subunit with RPC8; orthologue of yeast C17. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CRCP term: id: UniProtKB:O75575 label: DNA-directed RNA polymerase III subunit RPC9 - id: pol3_polr3k label: POLR3K role: RPC10 (RPC11), TFIIS-like subunit for RNA cleavage during backtracking and for termination. participant: selector_type: GENE_PRODUCT gene_product: preferred_term: POLR3K term: id: UniProtKB:Q9Y2Y1 label: DNA-directed RNA polymerase III subunit RPC10 function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity processes: - preferred_term: transcription elongation by RNA polymerase III term: id: GO:0006385 label: transcription elongation by RNA polymerase III - preferred_term: termination of RNA polymerase III transcription term: id: GO:0006386 label: termination of RNA polymerase III transcription locations: - preferred_term: nucleoplasm term: id: GO:0005654 label: nucleoplasm role_description: >- One complex annoton with 17 active units, as for Pol I in modules/rna_polymerase_i_transcription.yaml. The RPC7 position is a FAMILY unit whose two representative members are the paralogues POLR3G and POLR3GL; an enzyme contains one or the other. The catalytic subunits carry DNA-directed RNA polymerase activity (IDA, PMID:34675218); RPC3 and RPC6 carry their IDA single- and double-stranded DNA binding (PMID:21358628), which underlies promoter opening. The seven subunits shared with Pol I are listed with the same accessions in the Pol I module. evidence: - source_id: PMID:21358628 statement: Human Pol III has 17 subunits; RPC3, RPC6 and RPC7 form a heterotrimer required for promoter-specific initiation. supporting_text: hPol III subunits hRPC62, hRPC39 and hRPC32 form a stable ternary subcomplex required for promoter-specific transcription initiation by hPol III. - source_id: PMID:33558764 statement: Human Pol III can incorporate either RPC7 paralogue. supporting_text: human Pol III can utilise different isoforms of RPC7 (also known as POLR3G and hRPC32) - source_id: PMID:34675218 statement: Pol III terminates at a run of thymidines on the non-template strand without the trans-acting factors Pol I and Pol II need. supporting_text: By contrast, termination of Pol III-mediated transcription occurs when the polymerase reaches a stretch of more than three deoxythymidine nucleotides (poly-dT) on the non-template strand (strandNT), suggesting a Pol III-specific termination mechanism - source_id: PMID:12482973 statement: CGRP-RCP (CRCP) is the human RPC9 (yeast C17) subunit and is present in purified human Pol III. supporting_text: CGRP-RCP was identified by mass spectrometry in a highly purified human Pol III preparation. - order: 4 optional: true role: repression under nutrient limitation and stress node: id: maf1_repression label: MAF1 represses Pol III module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: negative regulation of transcription by RNA polymerase III term: id: GO:0016480 label: negative regulation of transcription by RNA polymerase III annotons: - id: maf1_pol3_inhibition label: Dephosphorylated MAF1 binds Pol III and blocks its recruitment by TFIIIB participant: selector_type: GENE_PRODUCT gene_product: preferred_term: MAF1 term: id: UniProtKB:Q9H063 label: Repressor of RNA polymerase III transcription MAF1 homolog function: preferred_term: RNA polymerase inhibitor activity term: id: GO:0140870 label: RNA polymerase inhibitor activity processes: - preferred_term: negative regulation of transcription by RNA polymerase III term: id: GO:0016480 label: negative regulation of transcription by RNA polymerase III locations: - preferred_term: nucleus term: id: GO:0005634 label: nucleus role_description: >- mTORC1 phosphorylation keeps MAF1 inactive; on mTOR inhibition or stress the dephosphorylated protein accumulates in the nucleus, occupies Pol III genes and displaces Pol III and BRF1. The function is curator-authored: GOA's experimental MAF1 molecular-function rows are type 1, 2 and 3 promoter DNA binding from ChIP occupancy (PMID:20233713), which describe where MAF1 is found rather than what it does, and its IBA row is RNA polymerase III core binding; RNA polymerase inhibitor activity follows the repression by binding the polymerase seen in the yeast Pol III-Maf1 structure discussed in PMID:33558764 and the IDA process rows for negative regulation of Pol III transcription. evidence: - source_id: PMID:20233713 statement: mTOR inhibition raises MAF1 occupancy of Pol III genes and lowers Pol III and BRF1 binding. supporting_text: mTOR inhibition led to an increase in the occupancy of Maf1 on a set of Pol III-dependent genes, with concomitant reduction in the binding of Pol III and Brf1. - source_id: PMID:17499043 statement: MAF1 occupancy of Pol III genes is reciprocal to that of TFIIIB and Pol III. supporting_text: Maf1 occupancy of Pol III genes is inversely correlated with that of the initiation factor TFIIIB and Pol III. - source_id: PMID:33558764 statement: RPC7-alpha may make Pol III resistant to MAF1, linking paralogue choice to repression. supporting_text: We hypothesise that the RPC7α subunit specifically protects against Maf1-mediated Pol III inhibition in tumour cells connections: - source: promoter_recognition target: tfiiib_recruitment connection_type: PRECEDES description: TFIIIC (types 1 and 2) or SNAPc (type 3) places TFIIIB upstream of the start site; SNAPc and BRF2-TFIIIB bind cooperatively. - source: tfiiib_recruitment target: pol3_transcription connection_type: PRECEDES description: BRF1 or BRF2 recruits Pol III, which opens the promoter without ATP hydrolysis and initiates. - source: maf1_pol3_inhibition target: pol3_enzyme connection_type: NEGATIVELY_REGULATES description: MAF1 binds Pol III and prevents its recruitment to promoter-bound TFIIIB.