RNA polymerase III is one of three types of nuclear RNA polymerases present in eucaryotic cells. About 10% of the total transcription in dividing cells can be attributed to its activity. It synthesizes an eclectic collection of catalytic or structural RNA molecules, some of which are involved in protein synthesis, pre-mRNA splicing, tRNA processing, and the control of RNA polymerase II elongation, whereas some others have still unknown functions. Like other RNA polymerases, RNA polymerase III cannot recognize its target promoters directly. Instead it is recruited to specific promoter sequences through the help of transcription factors. There are three basic types of RNA polymerase III promoters, called types 1, 2, and 3(Geiduschek and Kassavetis, 1992). Although in vivo, RNA polymerase III may be recruited to these promoters as part of a large complex (holo RNA polymerase III) containing the polymerase and its initiation factors (Wang et al., 1997), in vitro the reaction can be divided into several steps. First, the promoter elements are recognized by DNA binding factors, which then recruit a factor known as TFIIIB. TFIIIB itself then directly contacts RNA polymerase III. In human cells but not in S. cerevisiae, there are at least two versions of TFIIIB. One contains TBP, Bdp1, and Brf1 (Brf1-TFIIIB), and the other TBP, Bdp1, and Brf2 (Brf2-TFIIIB) (Schramm et al., 2000; Teichmann et al., 2000).
View original pathway at Reactome.
Teichmann M, Wang Z, Roeder RG.; ''A stable complex of a novel transcription factor IIB- related factor, human TFIIIB50, and associated proteins mediate selective transcription by RNA polymerase III of genes with upstream promoter elements.''; PubMedEurope PMCScholia
Wang Z, Bai L, Hsieh YJ, Roeder RG.; ''Nuclear factor 1 (NF1) affects accurate termination and multiple-round transcription by human RNA polymerase III.''; PubMedEurope PMCScholia
Brun I, Sentenac A, Werner M.; ''Dual role of the C34 subunit of RNA polymerase III in transcription initiation.''; PubMedEurope PMCScholia
Wang Z, Roeder RG.; ''DNA topoisomerase I and PC4 can interact with human TFIIIC to promote both accurate termination and transcription reinitiation by RNA polymerase III.''; PubMedEurope PMCScholia
Werner M, Chaussivert N, Willis IM, Sentenac A.; ''Interaction between a complex of RNA polymerase III subunits and the 70-kDa component of transcription factor IIIB.''; PubMedEurope PMCScholia
Zhao X, Pendergrast PS, Hernandez N.; ''A positioned nucleosome on the human U6 promoter allows recruitment of SNAPc by the Oct-1 POU domain.''; PubMedEurope PMCScholia
Stünkel W, Kober I, Seifart KH.; ''A nucleosome positioned in the distal promoter region activates transcription of the human U6 gene.''; PubMedEurope PMCScholia
Yoo CJ, Wolin SL.; ''La proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a yeast homolog of the La autoantigen is dispensable for growth.''; PubMedEurope PMCScholia
Khoo B, Brophy B, Jackson SP.; ''Conserved functional domains of the RNA polymerase III general transcription factor BRF.''; PubMedEurope PMCScholia
Hu P, Wu S, Sun Y, Yuan CC, Kobayashi R, Myers MP, Hernandez N.; ''Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits.''; PubMedEurope PMCScholia
Kassavetis GA, Nguyen ST, Kobayashi R, Kumar A, Geiduschek EP, Pisano M.; ''Cloning, expression, and function of TFC5, the gene encoding the B" component of the Saccharomyces cerevisiae RNA polymerase III transcription factor TFIIIB.''; PubMedEurope PMCScholia
Flores O, Lu H, Killeen M, Greenblatt J, Burton ZF, Reinberg D.; ''The small subunit of transcription factor IIF recruits RNA polymerase II into the preinitiation complex.''; PubMedEurope PMCScholia
Wong MW, Henry RW, Ma B, Kobayashi R, Klages N, Matthias P, Strubin M, Hernandez N.; ''The large subunit of basal transcription factor SNAPc is a Myb domain protein that interacts with Oct-1.''; PubMedEurope PMCScholia
Henry RW, Ma B, Sadowski CL, Kobayashi R, Hernandez N.; ''Cloning and characterization of SNAP50, a subunit of the snRNA-activating protein complex SNAPc.''; PubMedEurope PMCScholia
Wang Z, Luo T, Roeder RG.; ''Identification of an autonomously initiating RNA polymerase III holoenzyme containing a novel factor that is selectively inactivated during protein synthesis inhibition.''; PubMedEurope PMCScholia
Ma B, Hernandez N.; ''A map of protein-protein contacts within the small nuclear RNA-activating protein complex SNAPc.''; PubMedEurope PMCScholia
Dumay-Odelot H, Marck C, Durrieu-Gaillard S, Lefebvre O, Jourdain S, Prochazkova M, Pflieger A, Teichmann M.; ''Identification, molecular cloning, and characterization of the sixth subunit of human transcription factor TFIIIC.''; PubMedEurope PMCScholia
Mittal V, Ma B, Hernandez N.; ''SNAP(c): a core promoter factor with a built-in DNA-binding damper that is deactivated by the Oct-1 POU domain.''; PubMedEurope PMCScholia
Bartholomew B, Durkovich D, Kassavetis GA, Geiduschek EP.; ''Orientation and topography of RNA polymerase III in transcription complexes.''; PubMedEurope PMCScholia
Wang Z, Roeder RG.; ''Three human RNA polymerase III-specific subunits form a subcomplex with a selective function in specific transcription initiation.''; PubMedEurope PMCScholia
Matsuzaki H, Kassavetis GA, Geiduschek EP.; ''Analysis of RNA chain elongation and termination by Saccharomyces cerevisiae RNA polymerase III.''; PubMedEurope PMCScholia
Yoon JB, Murphy S, Bai L, Wang Z, Roeder RG.; ''Proximal sequence element-binding transcription factor (PTF) is a multisubunit complex required for transcription of both RNA polymerase II- and RNA polymerase III-dependent small nuclear RNA genes.''; PubMedEurope PMCScholia
Schramm L, Pendergrast PS, Sun Y, Hernandez N.; ''Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters.''; PubMedEurope PMCScholia
Kassavetis GA, Braun BR, Nguyen LH, Geiduschek EP.; ''S. cerevisiae TFIIIB is the transcription initiation factor proper of RNA polymerase III, while TFIIIA and TFIIIC are assembly factors.''; PubMedEurope PMCScholia
Schramm L, Hernandez N.; ''Recruitment of RNA polymerase III to its target promoters.''; PubMedEurope PMCScholia
These short oligonucleotides, principally di- and tri-nucleotides, are successfully elongated or are released from the DNA template Pol III complex by abortive initiation and RNA polymerase III retractive RNase activity at U-tract pause sites.
These short oligonucleotides, principally di- and tri-nucleotides, are successfully elongated or are released from the DNA template Pol III complex by abortive initiation and RNA polymerase III retractive RNase activity at U-tract pause sites.
Abortive initiation, the repetitive formation of short oligonucleotides, is a ubiquitous feature of transcriptional initiation. This event is inferred from an event in Saccharomyces cerevisiae.
Abortive initiation, the repetitive formation of short oligonucleotides, is a ubiquitous feature of transcriptional initiation. This event is inferred from an event in Saccharomyces cerevisiae.
Abortive initiation, the repetitive formation of short oligonucleotides, is a ubiquitous feature of transcriptional initiation. This event is inferred from an event in Saccharomyces cerevisiae.
Pol III initiation complexes open the promoter spontaneously. Indeed, this is the general case for DNA-dependent RNA polymerases. Only pol II, with its requirement for TFIIH-directed and ATP-dependent promoter opening is exceptional. TFIIH introduces a layer of mechanism that is not in the repertoire of any other transcriptase. Thus, it is pol III-mediated transcription that is, from a mechanistic perspective, most directly comparable with archaeal and also bacterial transcription.
As promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
Pol III initiation complexes open the promoter spontaneously. Indeed, this is the general case for DNA-dependent RNA polymerases. Only pol II, with its requirement for TFIIH-directed and ATP-dependent promoter opening is exceptional. TFIIH introduces a layer of mechanism that is not in the repertoire of any other transcriptase. Thus, it is pol III-mediated transcription that is, from a mechanistic perspective, most directly comparable with archaeal and also bacterial transcription.
As promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
Transcription by pol III initiates at characteristic, simple start sequences. The universal core of these start sites is a pyrimidine-purine step, transcription initiating most frequently with ATP or GTP. This event is inferred from an event in Saccharomyces cerevisiae.
Transcription by pol III initiates at characteristic, simple start sequences. The universal core of these start sites is a pyrimidine-purine step, transcription initiating most frequently with ATP or GTP. This event is inferred from an event in Saccharomyces cerevisiae.
Transcription by pol III initiates at characteristic, simple start sequences. The universal core of these start sites is a pyrimidine-purine step, transcription initiating most frequently with ATP or GTP. This event is inferred from an event in Saccharomyces cerevisiae.
Productive transcription is accompanied by retractive RNase activity at U-tract pause sites and at the terminator. The principal cleavage products are dinucleotides, and they are produced in large stoichiometric excess over complete transcripts, despite the rapid overall rate of productive RNA chain elongation. This event is inferred from an event in Saccharomyces cerevisiae.
The transition from abortive to productive transcription may occur at bp +5. The primary transcripts of pol III-transcribed genes are short, ~90 to 120 nt for tRNA and 5s RNA genes (which constitute the great majority of products) and even the longest transcripts (e.g. the RNA of the signal recognition particles) are only ~500 nt. This event is inferred from an event in Saccharomyces cerevisiae.
RNA Polymerase III terminates transcription at extremely simple sites, consistent with its role in producing small transcripts. These sites are essentially "Tn" (in the non-transcribed strand).
The principal cleavage products are dinucleotides, and they are produced in large stoichiometric excess over complete transcripts. Overall productive RNA chain elongation proceeds quite rapidly. This event is inferred from an event in Saccharomyces cerevisiae.
Efficient transcript production requires efficient release of RNA polymerase at the terminator; slow release at the terminator of a short transcription unit quickly becomes rate limiting for transcription at steady state. Although pol III autonomously recognizes sequence terminators, proteins that help to rapidly detach pol III from the terminator can affect the productivity of transcription if they eliminate termination as the rate-limiting step.
La, NF1 family proteins, PC4 and topoisomerase I have been proposed as accessory pol III transcription factors that facilitate multi-cycle transcription by hspol III, and are hence described as positive regulators of termination.
The principal cleavage products are dinucleotides, and they are produced in large stoichiometric excess over complete transcripts. Overall productive RNA chain elongation proceeds quite rapidly. This event is inferred from an event in Saccharomyces cerevisiae.
TFIIIA contains nine C2H2 zinc fingers (Arakawa et al., 1995). It binds to both the ICR region of the 5S RNA genes and to 5S RNA to form the 7S storage ribonucleoprotein particle (Pelham and Brown, 1980). Upon TFIIIA binding to the 5S gene, the TFIIIA zinc fingers are aligned over the length of the ICR with the C-terminal zinc fingers in proximity to the 5 end, and the N-terminal zinc fingers in proximity to the 3 end, of the ICR. Zinc fingers 1-3 contact the C block within the ICR and have been reported to contribute most of the binding energy of the full-length protein (Clemens et al., 1992). However, TFIIIA fragments containing zinc fingers 4-9 bind to the A block and intermediate element within the ICR with affinities close to those of the full-length protein. This and other observations suggest that simultaneous binding by all nine TFIIIA zinc fingers requires energetically unfavorable distortions within the DNA, the protein, or both (Kehres et al., 1997).
Proteolytic and scanning electron microscopy studies indicate that S. cerevisiae TFIIIC consists of two globular domains separated by a flexible linker, one of which, designated tau B, binds strongly to the B box, and the other, designated tau A, binds weakly to the A box, of type 2 promoters (Schultz et al., 1989). DNA footprinting and protein-protein interaction studies (Hsieh et al., 1999a; Hsieh et al., 1999b; Kovelman and Roeder, 1992; Shen et al., 1996; Yoshinaga et al., 1989) support the models shown in the figure. The components of Brf1-TFIIIB (see TFIIIB entries) are shown in grey, and TFIIIA is shown in blue. Sites of strong protein-DNA cross-linking are indicated by small ovals. Black and grey rectangles show protein-protein contacts observed in human and S. cerevisiae TFIIIC subunits, respectively. The general arrangement of the TFIIIC subunits on type 1 and 2 promoters is strikingly similar (Bartholomew et al., 1990; Braun et al., 1992a).
On type 1 promoters, S. cerevisiae TFIIIA cross-links strongly to the A box and more weakly over most of the gene, suggesting that it extends over most of the gene (Braun et al., 1992a). Tfc3 is shifted downstream as compared to its position in the tRNA gene, with a main cross-link at the 3 end of the C box and another one further downstream. The Tfc6 subunit cross-links at the end of the gene, like in type 2 genes. There is no indication that the Tfc7 subunit contacts DNA in type 1 genes, but the Tfc1 subunit cross-links strongly upstream of the A box. The Tfc4 subunit crosslinks to sites around and upstream of the start site of transcription (Braun et al., 1992a).
Numerous protein-protein contacts between various TFIIIC subunits have been described, which are symbolized by small rectangles in the figure. The black rectangles indicate contacts identified with human TFIIIC subunits, the grey rectangles with S. cerevisiae TFIIIC subunits. Thus, Tfc7 interacts directly with Tfc1 (Manaud et al., 1998). TTFIIIC90 interacts with TFIIIC220, TFIIIC110, and TFIIIC63 (Hsieh et al., 1999). TFIIIC102 interacts with TFIIIC63 (Hsieh et al., 1999). Various TFIIIC subunits also interact directly with Brf1-TFIIIB subunits, as shown in the figure. These protein-protein contacts are discussed below.
Cross-linking experiments performed in the yeast system have shown that within the transcription initiation complex, eight RNA polymerase III subunits can be cross-linked to DNA (Bartholomew et al., 1993). The C34 subunit, which is known to be required specifically for transcription initiation but not elongation (Wang and Roeder, 1997; Werner et al., 1993), maps the furthest upstream of the transcription start site, in close proximity to Brf1-TFIIIB (Bartholomew et al., 1993). Indeed, this subunit interacts with Brf1 (Khoo et al., 1994; Werner et al., 1993). The figure illustrates this and other protein-protein contacts involving RNA polymerase III subunits and either TFIIIC or Brf1-TFIIIB subunits. The contacts identified with S. cerevisiae proteins are indicated by stippled arrows, those identified with human protein by solid arrows. Both the S. cerevisiae RNA polymerase III subunits C53 and ABC10a interact with Tfc4 ( 1999; Flores et al., 1999), and both C17 and C34 interact with Brf1. The human subunit RPC62 interacts with TIIIC63, and RPC39 with the TFIIIC subunits TFIIIC90 and TFIIIC63 (Hsieh et al., 1999a) and the Brf1-TFIIIB subunits Brf1 and TBP (Wang and Roeder, 1997). The contacts between RNA polymerase III and TFIIIC subunits are not absolutely required for transcription in vitro with the S. cerevisiae system, in which TFIIIC can be stripped from the DNA after assembly of TFIIIB without compromising transcription (Kassavetis et al., 1990) or, indeed, where transcription can be performed in the absence of TFIIIC on TATA box-containing promoters (Kassavetis et al., 1995). Nevertheless, they may contribute to the recruitment of RNA polymerase III in vivo.
Pol III initiation complexes open the promoter spontaneously. Indeed, this is the general case for DNA-dependent RNA polymerases. Only pol II, with its requirement for TFIIH-directed and ATP-dependent promoter opening is exceptional. TFIIH introduces a layer of mechanism that is not in the repertoire of any other transcriptase. Thus, it is pol III-mediated transcription that is, from a mechanistic perspective, most directly comparable with archaeal and also bacterial transcription.
As promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
The recruitment of Brf1-TFIIIB to type 1 and 2 promoters has been intensively studied in S. cerevisiae (Joazeiro et al., 1996). The Tfc4 subunit of TFIIIC, which protrudes upstream of the transcription start site (Bartholomew et al., 1990), can interact with the Brf1 subunit of Brf1-TFIIIB (Moir et al., 1997). The Tfc4 subunit, which contains 11 copies of the tetratricopeptide repeat (TPR), appears to undergo conformational changes during binding that promote association with ScBrf1 and accommodate variable placements of TFIIIB (Moir et al., 1997). As shown in the figure, a number of protein-protein associations involving both S. cerevisiae and human TFIIIC and TFIIIB subunits have been described, which may participate in the recruitment of TFIIIB to type 1 and 2 promoters. Thus, Tfc8 has been show to interact with Bdp1 and TBP, and the corresponding human protein TFIIIC90 with Brf1 (Hsieh et al., 1999); Tfc4 with Brf1 and Bdp1, and the corresponding human protein TFIIIC102 with Brf1 and TBP (Hsieh et al., 1999); and the human protein TFIIIC63 with Brf1 and TBP (Hsieh et al., 1999).
Proteolytic and scanning electron microscopy studies indicate that S. cerevisiae TFIIIC consists of two globular domains separated by a flexible linker, one of which, designated tau B, binds strongly to the B box, and the other, designated tau A, binds weakly to the A box, of type 2 promoters (Marzouki et al., 1986). DNA footprinting and protein-protein interaction studies (Hsieh et al., 1999; Hsieh et al., 1999; Kovelman and Roeder, 1992; Shen et al., 1996; Yoshinaga et al., 1989) support the models shown in the figure. The components of Brf1-TFIIIB (see TFIIIB entries) are shown in grey, and TFIIIA is shown in blue. Sites of strong protein-DNA cross-linking are indicated by small ovals. Black and grey rectangles show protein-protein contacts observed in human and S. cerevisiae TFIIIC subunits, respectively. The general arrangement of the TFIIIC subunits on type 1 and 2 promoters is strikingly similar (Bartholomew et al., 1990; Braun et al., 1992a).
On a type 2 promoter, the S. cerevisiae Tfc3 subunit cross-links primarily just upstream of the B box and Tfc6 cross-links at the end of the gene (Bartholomew et al., 1990). Tfc1 and Tfc7 have strong cross-links within and near the 3 end of the A box, respectively (Bartholomew et al., 1990). Tfc8 does not cross-link to DNA, and after partial protease digestion of TFIIIC, is found in the tB domain. In addition, however, Tfc8 displays genetic interactions with Tfc1, TBP, and ScBdp1, and it associates with TBP in vitro, suggesting that it is also present in the tA domain. The Tfc4 subunit cross-links to sites around and upstream of the transcription start site (Bartholomew et al., 1990) and directly contacts both the ScBrf1 and ScBdp1 subunits of TFIIIB.
Numerous protein-protein contacts between various TFIIIC subunits have been described, which are symbolized by small rectangles in the figure. The black rectangles indicate contacts identified with human TFIIIC subunits, the grey rectangles with S. cerevisiae TFIIIC subunits. Thus, Tfc7 interacts directly with Tfc1. TTFIIIC90 interacts with TFIIIC220, TFIIIC110, and TFIIIC63 (Hsieh et al., 1999). TFIIIC102 interacts with TFIIIC63 (Hsieh et al., 1999). Various TFIIIC subunits also interact directly with Brf1-TFIIIB subunits, as shown in the figure.
The recruitment of Brf1-TFIIIB to type 1 and 2 promoters has been intensively studied in S. cerevisiae (Joazeiro et al., 1996). The Tfc4 subunit of TFIIIC, which protrudes upstream of the transcription start site (Bartholomew et al., 1990), can interact with the Brf1 subunit of Brf1-TFIIIB (Moir et al., 1997). The Tfc4 subunit, which contains 11 copies of the tetratricopeptide repeat (TPR), appears to undergo conformational changes during binding that promote association with ScBrf1 and accommodate variable placements of TFIIIB (Moir et al., 1997). As shown in the figure, a number of protein-protein associations involving both S. cerevisiae and human TFIIIC and TFIIIB subunits have been described, which may participate in the recruitment of TFIIIB to type 1 and 2 promoters. Thus, Tfc8 has been show to interact with Bdp1 and TBP, and the corresponding human protein TFIIIC90 with Brf1 (Hsieh et al., 1999); Tfc4 with Brf1 and Bdp1, and the corresponding human protein TFIIIC102 with Brf1 and TBP (Hsieh et al., 1999); and the human protein TFIIIC63 with Brf1 and TBP (Hsieh et al., 1999).
SNAPc binds specifically to the PSE. This binding is mediated in part by an unusual Myb domain within SNAP190 (Mittal et al., 1999; Wong et al., 1998). However, even though a SNAP190 segment consisting of just the Myb domain binds DNA, within the complex the Myb domain is not sufficient for binding. The smallest characterized subassembly of SNAPc subunits that binds specifically to DNA consists of SNAP190 aa 84-505, SNAP43 aa 1-268, and SNAP50 (Ma and Hernandez, 2000). Consistent with the requirement for parts of SNAP190 and SNAP50 for DNA binding, UV cross-linking experiments suggest that both SNAP190 (Yoon et al., 1995) and SNAP50 (Henry et al., 1996) are in close contact with DNA.
The binding of SNAPc to the PSE is stabilized by a number of cooperative interactions with other members of the transcription initiation complex including Oct-1, TBP, and Brf2.
The binding of SNAPc to the core promoter is stabilized by a direct protein-protein contact with the Oct-1 POU domain.
SNAPc does not bind very efficiently to the PSE on its own. It contains a damper of DNA binding that resides within the C-terminal two thirds of SNAP190 and/or SNAP45, because a subcomplex of SNAPc (mini-SNAPc) lacking these sequences binds much more efficiently to DNA than complete SNAPc (Mittal et al., 1999). The damper within SNAPc is deactivated, probably through a conformational change, by a direct protein-protein contact with the Oct-1 POU domain. The transcription initiation complex is illustrated in Figure 6. The protein-protein contact between the Oct-1 POU domain and SNAPc involves a glutamic acid at position 7 within the Oct-1 POUS domain and a lysine at position 900 within SNAP190, which are symbolized in Figure 6 by small triangles (Ford et al., 1998; Hovde et al., 2002; Mittal et al., 1999). The octamer sequence within the DSE and the PSE are separated by more than 150 base pairs, but the direct protein-protein contact is rendered possible by the presence of a positioned nucleosome between the DSE and the PSE, which, as shown in the figure, probably brings into close proximity the Oct-1 POU domain and SNAPc (Stunkel et al., 1997; Zhao et al., 2001).
The snRNA activating protein complex (SNAPc) (Sadowski et al., 1993), the PSE binding protein (PBP) (Waldschmidt et al., 1991), or the PSE transcription factor (PTF) (Murphy et al., 1992). The complex contains five types of subunits and binds to the PSE. Type 3 promoters also recruit Brf2-TFIIIB through a combination of protein-protein contacts with SNAPc and a direct association of the TBP component of Brf2-TFIIIB with the TATA box. This then allows RNA polymerase III to join the complex.
The binding of SNAPc to the PSE is stabilized not only by cooperative interactions with the Oct-1 POU domain, but also by cooperative interactions with TBP and Brf2 (Hinkley et al., 2003 ; Ma and Hernandez, 2002; Mittal and Hernandez, 1997). Moreover, Brf2, which cannot bind to DNA on its own, recognizes and stabilizes TBP bound to the TATA box (Cabart and Murphy, 2001; Cabart and Murphy, 2002; Ma and Hernandez, 2002). Thus, the U6 transcription initiation complex is stabilized by a complex network of protein-protein and protein-DNA interactions. Nothing is known, however, about how the complex recruits RNA polymerase III.
At the beginning of this reaction, 1 molecule of 'TFIIIB:TFIIIC:Type 2 Promoter Complex', and 1 molecule of 'RNA Polymerase III Holoenzyme' are present. At the end of this reaction, 1 molecule of 'RNA Polymerase III:TFIIIB:TFIIIC:Type 2 Promoter Complex' is present.
This reaction takes place in the 'nucleus' (Hernandez 2002, Geiduschek and Kassavettis 2001).
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DataNodes
Polymerase III Type
1 Closed PromoterPolymerase III Type
2 Closed PromoterPolymerase III Type
3 Closed PromoterPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexDNA with a
termination sitePolymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Promoter ComplexPromoter Selective
ComplexPromoter Selective
ComplexPol III
oligonucleotidePol III transcript
plus 1 nucleotideAnnotated Interactions
Polymerase III Type
1 Closed PromoterPolymerase III Type
2 Closed PromoterPolymerase III Type
3 Closed PromoterPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexPolymerase III Transcription
ComplexDNA with a
termination siteAs promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
As promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
La, NF1 family proteins, PC4 and topoisomerase I have been proposed as accessory pol III transcription factors that facilitate multi-cycle transcription by hspol III, and are hence described as positive regulators of termination.
On type 1 promoters, S. cerevisiae TFIIIA cross-links strongly to the A box and more weakly over most of the gene, suggesting that it extends over most of the gene (Braun et al., 1992a). Tfc3 is shifted downstream as compared to its position in the tRNA gene, with a main cross-link at the 3 end of the C box and another one further downstream. The Tfc6 subunit cross-links at the end of the gene, like in type 2 genes. There is no indication that the Tfc7 subunit contacts DNA in type 1 genes, but the Tfc1 subunit cross-links strongly upstream of the A box. The Tfc4 subunit crosslinks to sites around and upstream of the start site of transcription (Braun et al., 1992a).
Numerous protein-protein contacts between various TFIIIC subunits have been described, which are symbolized by small rectangles in the figure. The black rectangles indicate contacts identified with human TFIIIC subunits, the grey rectangles with S. cerevisiae TFIIIC subunits. Thus, Tfc7 interacts directly with Tfc1 (Manaud et al., 1998). TTFIIIC90 interacts with TFIIIC220, TFIIIC110, and TFIIIC63 (Hsieh et al., 1999). TFIIIC102 interacts with TFIIIC63 (Hsieh et al., 1999). Various TFIIIC subunits also interact directly with Brf1-TFIIIB subunits, as shown in the figure. These protein-protein contacts are discussed below.
As promoter opening has been analyzed only in the S. cerevisiae this event is Inferred from the homologous pathway in yeast.
On a type 2 promoter, the S. cerevisiae Tfc3 subunit cross-links primarily just upstream of the B box and Tfc6 cross-links at the end of the gene (Bartholomew et al., 1990). Tfc1 and Tfc7 have strong cross-links within and near the 3 end of the A box, respectively (Bartholomew et al., 1990). Tfc8 does not cross-link to DNA, and after partial protease digestion of TFIIIC, is found in the tB domain. In addition, however, Tfc8 displays genetic interactions with Tfc1, TBP, and ScBdp1, and it associates with TBP in vitro, suggesting that it is also present in the tA domain. The Tfc4 subunit cross-links to sites around and upstream of the transcription start site (Bartholomew et al., 1990) and directly contacts both the ScBrf1 and ScBdp1 subunits of TFIIIB.
Numerous protein-protein contacts between various TFIIIC subunits have been described, which are symbolized by small rectangles in the figure. The black rectangles indicate contacts identified with human TFIIIC subunits, the grey rectangles with S. cerevisiae TFIIIC subunits. Thus, Tfc7 interacts directly with Tfc1. TTFIIIC90 interacts with TFIIIC220, TFIIIC110, and TFIIIC63 (Hsieh et al., 1999). TFIIIC102 interacts with TFIIIC63 (Hsieh et al., 1999). Various TFIIIC subunits also interact directly with Brf1-TFIIIB subunits, as shown in the figure.
The binding of SNAPc to the PSE is stabilized by a number of cooperative interactions with other members of the transcription initiation complex including Oct-1, TBP, and Brf2.
The binding of SNAPc to the core promoter is stabilized by a direct protein-protein contact with the Oct-1 POU domain.
SNAPc does not bind very efficiently to the PSE on its own. It contains a damper of DNA binding that resides within the C-terminal two thirds of SNAP190 and/or SNAP45, because a subcomplex of SNAPc (mini-SNAPc) lacking these sequences binds much more efficiently to DNA than complete SNAPc (Mittal et al., 1999). The damper within SNAPc is deactivated, probably through a conformational change, by a direct protein-protein contact with the Oct-1 POU domain. The transcription initiation complex is illustrated in Figure 6. The protein-protein contact between the Oct-1 POU domain and SNAPc involves a glutamic acid at position 7 within the Oct-1 POUS domain and a lysine at position 900 within SNAP190, which are symbolized in Figure 6 by small triangles (Ford et al., 1998; Hovde et al., 2002; Mittal et al., 1999). The octamer sequence within the DSE and the PSE are separated by more than 150 base pairs, but the direct protein-protein contact is rendered possible by the presence of a positioned nucleosome between the DSE and the PSE, which, as shown in the figure, probably brings into close proximity the Oct-1 POU domain and SNAPc (Stunkel et al., 1997; Zhao et al., 2001).
This reaction takes place in the 'nucleus' (Hernandez 2002, Geiduschek and Kassavettis 2001).
Polymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Open Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Promoter ComplexPolymerase
III:TFIIIB:SNAPc:Type 3 Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Open Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Promoter ComplexPolymerase
III:TFIIIB:TFIIIC:Type 2 Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Open Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Promoter Complexpolymerase
III:TFIIIB:TFIIIC:TFIIIA:Type 1 Promoter ComplexPromoter Selective
ComplexPromoter Selective
ComplexPromoter Selective
ComplexPol III
oligonucleotidePol III
oligonucleotidePol III
oligonucleotidePol III
oligonucleotidePol III
oligonucleotidePol III
oligonucleotidePol III
oligonucleotidePol III transcript
plus 1 nucleotidePol III transcript
plus 1 nucleotide