RPC10/YHR143W-A Summary Help

Standard Name RPC10 1
Systematic Name YHR143W-A
Alias RPB12 2
Feature Type ORF, Verified
Description RNA polymerase subunit ABC10-alpha, found in RNA pol I, II, and III; relocalizes from nucleolus to cytoplasm upon DNA replication stress (3, 4, 5 and see Summary Paragraph)
Name Description RNA Polymerase C 6
Gene Product Alias ABC10-alpha 4
Chromosomal Location
ChrVIII:387233 to 387445 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All RPC10 GO evidence and references
  View Computational GO annotations for RPC10
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
conditional
null
Large-scale survey
null
repressible
Resources
93 total interaction(s) for 64 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 56
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 4
  • Co-crystal Structure: 2
  • Co-purification: 1
  • Far Western: 1
  • PCA: 4
  • Two-hybrid: 4

Genetic Interactions
  • Dosage Lethality: 3
  • Dosage Rescue: 7
  • Synthetic Growth Defect: 2
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 1
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 70
Molecular Weight (Da) 7,716
Isoelectric Point (pI) 10.5
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:387233 to 387445 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..213 387233..387445 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001185
SUMMARY PARAGRAPH for RPC10

Nuclear transcription in S. cerevisiae is performed by three multisubunit nuclear RNA polymerases (RNAPs) that are conserved in all eukaryotes (7, 8 and references therein). The roles of these three RNA polymerases are generally conserved across eukaryotes, particularly with respect to production of rRNAs, mRNAs, and tRNAs, though production of other small RNAs is somewhat variable between RNAP II and RNAP III in different species (9). In S. cerevisiae, RNA polymerase I transcribes rDNA to produce the 35S primary rRNA transcript that is processed to produce three of the four mature ribosomal rRNAs: 25S, 18S, and 5.8S. RNA polymerase II produces all nuclear mRNAs, all of the snoRNAs except snR52 (10), four of the five snRNAs (U1, U2, U4, and U5; 11), the RNase MRP RNA encoded by NME1 (9), and the telomerase RNA encoded by TLC1 (12). RNA polymerase III produces the 5S rRNA, all nuclear tRNAs, the U6 snRNA (13), the snR52 snoRNA (10), the RNase P RNA encoded by RPR1 (9), and the 7SL RNA component of the signal recognition particle encoded by SCR1 (9).

Coordinate regulation of these three RNA polymerases is essential, since in rapidly growing yeast cells, much of the transcriptional output of the cell is devoted to the production of ribosomes. About 60% of total cellular transcription is devoted to transcription by RNAP I of the rRNA genes, which comprise about 10% of the entire genome. While mRNAs generally only comprise 5% of total cellular RNA and the 137 ribosomal protein (RP) genes represent only 2% of the genome, it is estimated that 50% of RNAP II transcription occurs on RP genes. RNAP II is also responsible for production of the majority of the snoRNAs, which are collectively involved in maturation of the ribosome. RNAP III plays a similarly important role in production of ribosomes and the process of translation, producing both the 5S rRNA and all nuclear tRNAs, which constitute about 15% of total cellular RNA (reviewed in 14). The TOR pathway is a major factor in this coordinate regulation as it regulates the activity of all three nuclear RNAPs in response to nutrient availability and growth conditions (reviewed in 15, 16, 17, and 18).

In addition to producing the majority of cellular RNA, RNAP I and RNAP III may also play roles in nuclear architecture and genome organization. RNAP I activity may be involved in organizing the rDNA repeats into the nucleolus (reviewed in 19). Active tRNA genes transcribed by RNAP III appear to act as chromatin boundary elements that affect both transcription and DNA replication. Additionally, recombination between dispersed tRNA genes may be a source of genetic instability and evolutionary change (reviewed in 20).

Five genes (RPB5, RPO26, RPB8, RPB10, and RPC10) encode subunits common to all three of the nuclear RNA polymerases. Two genes (RPC40 and RPC19) encode subunits present in both RNAP I and RNAP III; RPB3 and RPB11 encode the corresponding RNAP II subunits. Five more subunits are encoded by a separate gene for each polymerase, but are considered functional equivalents of each other. Thus there are twelve subunits that are conserved in all three of the nuclear RNA polymerases, eleven of which correspond to subunits of Archaeal RNAPs, and five of which also correspond to the subunits of E. coli RNAP. In each, ten of these comprise the enzyme cores, while Rpb4/7 (RNAP II), Rpa14/43 (RNAP I), and Rpc17/25 (RNAP III) form heterodimers which associate with this core and have roles in initiation (21). RNAPs I and III also have two subunits which are homologous to the subunits of the TFIIF general initiation factor for RNAP II, and RNAP III has three additional unique subunits (reviewed in 22, 8, and 23). For tables showing the correspondence between the subunits of the three nuclear RNA polymerases in S. cerevisiae see Cramer et al. 2008 (23) and Werner et al. 2009 (22); to see the correspondence with those of Archaea and bacteria see Cramer 2002 (8).

About RNA polymerase I

In S. cerevisiae, the RNA polymerase I enzyme is composed of fourteen subunits. RPB5, RPO26, RPB8, RPC10, RPB10, RPC40, and RPC19 encode subunits shared with one or both of the other two nuclear RNA polymerases. RPA49 and RPA34 encode subunits with counterparts in RNA polymerase III and RPA190, RPA135, RPA43, RPA14, and RPA12 encode subunits with counterparts in both RNA polymerases II and III (24, 25, and reviewed in 21).

Most of the genes encoding subunits of RNA polymerase I are essential (26 and references therein) and elegant genetic experiments have shown that production of the large rRNA transcript is the only essential role of these genes (reviewed in 27). However, null mutations in any of four of the genes (RPA49, RPA34, RPA14, and RPA12) encoding subunits present only in RNAP I produce viable strains. While a triple mutant strain lacking functional RPA49, RPA34, and RPA12 is viable, inactivating any one of these genes in combination with RPA14 is lethal. Thus these four subunits are dispensible individually but collectively become essential (28). Rpa49p and Rpa34p, as expected from their similarity to TFIIF, contribute to the elongation properties of RNAP I (21). Rpa12p contains a C-terminal domain with similarity to the RNAP II elongation factor TFIIS (encoded by DST1) which appears to activate the transcript cleavage activity intrinsic to the RNAP I catalytic core (21). Mutations in core subunits such as RPA190, RPA135, RPC40, and RPC19 often affect the basic functions of core enzyme assembly and catalytic properties of initiation, elongation, or termination, as well as the association of the core enzyme with the other complexes required for RNAP I function in vivo (26 and references therein).

RNAP I transcription requires a number of factors in addition to the polymerase itself: TATA-binding protein (TBP, encoded by SPT15), the initiation factor Rrn3 (homologous to mammalian TIF-IA), the core factor CF (composed of Rrn6p, Rrn7p, and Rrn11p), and the upstream activating factor UAF (composed of Rrn5p, Rrn9p, Rrn10p, Uaf30p, and histones H3 and H4). While some of these factors have mammalian homologs, others are more diverged, as might be expected from the fact that there is little conservation of rDNA promoter sequences across taxonomic groupings although some structural elements are conserved (reviewed in 27 and 15). UAF binds to the promoter and recruits CF and a complex of Rrn3p associated with RNAP I. Rrn3p plays a key role in the regulation of RNAP I activity, as RNAP I is only able to initiate transcription when it is associated with Rrn3p, but any of the RNAP I transcription factors may serve as a target for regulation. In addition, the TFIIH factor, originally characterized as a RNAP II transcription factor, is also required for productive transcriptional elongation by RNAP I and for coupling of DNA repair to rDNA transcription. Numerous regulatory pathways are involved in the complex regulation of RNAP I in response to growth signals, including both the TOR and MAP kinase signaling pathways and chromatin remodeling activities (reviewed in 16, 15 and 18). Thus control of RNAP I activity is central to control of ribosome production and growth control in S. cerevisiae.

About RNA polymerase II

In S. cerevisiae, the RNA polymerase II core enzyme (RNAP II) is composed of twelve subunits. RPO21, RPB2, RPB3, RPB4, RPB7, RPB9, and RPB11 encode subunits unique to RNAP II, while RPB5, RPO26, RPB8, RPC10, and RPB10 encode shared subunits (8). A subcomplex composed of Rpb4p and Rpb7p (Rpb4/7) is substoichiometric in some growth conditions and easily dissociated during purification (29, 30). Purified enzyme composed of the remaining 10 subunits is capable of polymerizing RNA in vitro, but does not recognize or initiate at promoter sequences (31, 29). The structure of the core enzyme has been determined, with and without the Rpb4/7 subcomplex, and provides insight into the specific roles of the subunits within the complex (32, 33, 8 and references therein).

Most of the genes encoding subunits of RNA polymerase II are essential (26 and references therein). However null mutations in rpb4 or rpb9 are not essential in standard laboratory conditions, but become so when cells are subjected to stresses such as reduced or elevated temperature or absence of nutrients such as inositol. While not required for catalytic activity, Rpb4p as part of the Rpb4/7 subcomplex is required for response to heat or cold stress, recovery from stationary phase, and sporulation, and is also thought to be involved in response to transcriptional activators, mRNA export during heat stress, and regulation of transcription coupled repair (34). Also not required for catalytic activity, Rpb9p is involved in selection of the transcription initiation site and control of fidelity (35; 36). Partial truncations of the carboxyl terminal domain (CTD) of the largest subunit RPO21, or conditional mutations in one of the essential subunits, may also produce the combined phenotype of cold sensitivity, heat sensitivity and inositol auxotrophy. This combination of phenotypes appears to be due to sensitivity of specific genes, such as INO1, to reduction in the function or quantity of RNAP II (37). Mutations in core subunits such as RPO21, RPB2, or RPB3 often affect the basic functions of core enzyme assembly and catalytic properties of initiation, elongation, or termination, as well as the association of the core enzyme with the other complexes required for RNAP II function in vivo (26 and references therein).

In yeast, as in other eukaryotes, fully competent RNA polymerase II activity in vivo requires the association of the full core enzyme with several other complexes, including the general transcription factors (GTFs) TFIID, TFIIB, TFIIF, TFIIE, and TFIIH. Some of the GTFs bind directly to DNA to identify the promoter sequence and recruit the remaining GTFs and RNAP II to the promoter to form the preinitiation complex (PIC). In addition, Mediator, a large modular complex, is required for RNAP II to respond to gene-specific activators. Some of these factors travel with RNAP II along the transcription unit. When purified together, RNAP II and Mediator are sometimes referred to as "holoenzyme", though it appears that multiple "holoenzymes" have been purified with slightly varied subunit composition depending on the purification method, which may reflect the modular nature of Mediator as well as the need to respond to different regulatory signals (38 and references therein).

The largest subunit RPO21 contains a repetitive carboxyl terminal domain (CTD), unique to type II RNA polymerases, composed of numerous copies of the seven-amino-acid sequence YSPTSPS. Though the number of repeats varies between the largest subunits of different species, deletion of the entire CTD is invariably lethal even though it is not required in vitro for catalytic activity (31, 39). The CTD undergoes cycles of phosphorylation and dephosphorylation, especially on serines 2 and 5. Its phosphorylation state regulates interactions of the core enzyme with other protein complexes such as the GTFs, Mediator, and chromatin remodelling enzymes, thus regulating both initiation and elongation in vivo (38, 39). During production of the primary transcript, the phosphorylation state of the CTD changes to allow the transcribing polymerase to associate with the capping, splicing, polyadenylation, and mRNA export machinery (39). These associations are required for normal processing of pre-mRNAs to generate mRNAs and to export them to the cytoplasm, as well as for normal termination of transcription by RNAP II (40). Thus the CTD plays essential roles in the coordinate regulation of gene expression, mRNA production, and the export of mRNAs to the cytoplasm.

About RNA polymerase III

In S. cerevisiae, the RNA polymerase III enzyme is composed of seventeen subunits, all of which are essential. RPB5, RPO26, RPB8, RPC10, RPB10, RPC40, and RPC19 encode subunits shared with one or both of the other two nuclear RNA polymerases. RPC53 and RPC37 encode subunits with counterparts in RNAP I, and RPO31, RET1, RPC25, RPC17, and RPC11 encode subunits with counterparts in both RNA polymerases I and II. RPC82, RPC34, and RPC31 encode subunits unique to RNAP III and homologous to a detachable subassembly of human RNAP III implicated in response to specific transcription factors (reviewed in 41, 42, 23, and 22).

In contrast to RNAP I and II promoters, most RNAP III promoters are internal to the expressed sequence of the RNA being transcribed, though there are some exceptions such as the well studied U6 snRNA (encoded by snR6). These internal promoters can be divided into classes based on their organization. Class 1 genes are represented by the 5S rRNA genes, present within the intragenic spacer of the 37S rDNA, and are the only genes which require the specific DNA-binding initiation factor TFIIIA (encoded by PZF1), the archetype zinc finger protein, which then recruits TFIIIC. Class 2 genes comprise the tRNA genes, and others with similar promoter structures, containing internal box A and box B sequence elements which are recognized directly by the six subunit DNA-binding initiation factor TFIIIC (encoded by TFC1, TFC3, TFC4, TFC6, TFC7, and TFC8). In both classes, TFIIIC recruits TFIIIB, which does not bind to DNA by itself despite the fact that it contains the TATA-binding protein TBP (encoded by SPT15), as well as two other subunits (BDP1 and BRF1). Once bound to DNA, TFIIIB brings RNAP III to the promoter and helps initiate transcription (reviewed in 41, 43, and 22). RNAP III transcription is regulated by at least two nutrient-sensing signal transduction pathways, RAS and TOR. Both of these work through Maf1p, which is evolutionarily conserved from yeast to humans, and which represses RNAP III activity when yeast cells experience stress or unfavorable growth conditions (reviewed in 44).

Last updated: 2010-02-04 Contact SGD

References cited on this page View Complete Literature Guide for RPC10
1) Treich I, et al.  (1992) RPC10 encodes a new mini subunit shared by yeast nuclear RNA polymerases. Gene Expr 2(1):31-7
2) Sayre MH, et al.  (1992) Reconstitution of transcription with five purified initiation factors and RNA polymerase II from Saccharomyces cerevisiae. J Biol Chem 267(32):23376-82
3) Hampsey M  (1998) Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol Mol Biol Rev 62(2):465-503
4) Carles C, et al.  (1991) Two additional common subunits, ABC10 alpha and ABC10 beta, are shared by yeast RNA polymerases. J Biol Chem 266(35):24092-6
5) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
6) Nonet M, et al.  (1987) Eucaryotic RNA polymerase conditional mutant that rapidly ceases mRNA synthesis. Mol Cell Biol 7(5):1602-11
7) Sentenac A  (1985) Eukaryotic RNA polymerases. CRC Crit Rev Biochem 18(1):31-90
8) Cramer P  (2002) Multisubunit RNA polymerases. Curr Opin Struct Biol 12(1):89-97
9) Dieci G, et al.  (2007) The expanding RNA polymerase III transcriptome. Trends Genet 23(12):614-22
10) Moqtaderi Z and Struhl K  (2004) Genome-wide occupancy profile of the RNA polymerase III machinery in Saccharomyces cerevisiae reveals loci with incomplete transcription complexes. Mol Cell Biol 24(10):4118-27
11) Xue D, et al.  (2000) U snRNP assembly in yeast involves the La protein. EMBO J 19(7):1650-60
12) Chapon C, et al.  (1997) Polyadenylation of telomerase RNA in budding yeast. RNA 3(11):1337-51
13) Eschenlauer JB, et al.  (1993) Architecture of a yeast U6 RNA gene promoter. Mol Cell Biol 13(5):3015-26
14) Warner JR  (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24(11):437-40
15) Grummt I  (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17(14):1691-702
16) Willis IM, et al.  (2004) Signaling repression of transcription by RNA polymerase III in yeast. Prog Nucleic Acid Res Mol Biol 77:323-53
17) Mayer C and Grummt I  (2006) Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25(48):6384-91
18) Xiao L and Grove A  (2009) Coordination of Ribosomal Protein and Ribosomal RNA Gene Expression in Response to TOR Signaling. Curr Genomics 10(3):198-205
19) Shaw P and Doonan J  (2005) The nucleolus. Playing by different rules? Cell Cycle 4(1):102-5
20) McFarlane RJ and Whitehall SK  (2009) tRNA genes in eukaryotic genome organization and reorganization. Cell Cycle 8(19):3102-6
21) Kuhn CD, et al.  (2007) Functional architecture of RNA polymerase I. Cell 131(7):1260-72
22) Werner M, et al.  (2009) Structure-function analysis of RNA polymerases I and III. Curr Opin Struct Biol 19(6):740-5
23) Cramer P, et al.  (2008) Structure of eukaryotic RNA polymerases. Annu Rev Biophys 37():337-52
24) Panov KI, et al.  (2006) RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor. Mol Cell Biol 26(14):5436-48
25) Beckouet F, et al.  (2008) Two RNA Polymerase I Subunits Control the Binding and Release of Rrn3 during Transcription. Mol Cell Biol 28(5):1596-1605
26) Archambault J and Friesen JD  (1993) Genetics of eukaryotic RNA polymerases I, II, and III. Microbiol Rev 57(3):703-24
27) Reeder RH  (1999) Regulation of RNA polymerase I transcription in yeast and vertebrates. Prog Nucleic Acid Res Mol Biol 62:293-327
28) Gadal O, et al.  (1997) A34.5, a nonessential component of yeast RNA polymerase I, cooperates with subunit A14 and DNA topoisomerase I to produce a functional rRNA synthesis machine. Mol Cell Biol 17(4):1787-95
29) Edwards AM, et al.  (1991) Two dissociable subunits of yeast RNA polymerase II stimulate the initiation of transcription at a promoter in vitro. J Biol Chem 266(1):71-5
30) Choder M and Young RA  (1993) A portion of RNA polymerase II molecules has a component essential for stress responses and stress survival. Mol Cell Biol 13(11):6984-91
31) Christie KR, et al.  (1994) Purified yeast RNA polymerase II reads through intrinsic blocks to elongation in response to the yeast TFIIS analogue, P37. J Biol Chem 269(2):936-43
32) Meyer PA, et al.  (2009) Structure of the 12-subunit RNA polymerase II refined with the aid of anomalous diffraction data. J Biol Chem 284(19):12933-9
33) Armache KJ, et al.  (2005) Structures of complete RNA polymerase II and its subcomplex, Rpb4/7. J Biol Chem 280(8):7131-4
34) Sampath V and Sadhale P  (2005) Rpb4 and Rpb7: a sub-complex integral to multi-subunit RNA polymerases performs a multitude of functions. IUBMB Life 57(2):93-102
35) Hull MW, et al.  (1995) RNA polymerase II subunit RPB9 is required for accurate start site selection. Genes Dev 9(4):481-90
36) Walmacq C, et al.  (2009) Rpb9 Subunit Controls Transcription Fidelity by Delaying NTP Sequestration in RNA Polymerase II. J Biol Chem 284(29):19601-12
37) Archambault J, et al.  (1996) Underproduction of the largest subunit of RNA polymerase II causes temperature sensitivity, slow growth, and inositol auxotrophy in Saccharomyces cerevisiae. Genetics 142(3):737-47
38) Woychik NA and Hampsey M  (2002) The RNA polymerase II machinery: structure illuminates function. Cell 108(4):453-63
39) Phatnani HP and Greenleaf AL  (2006) Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev 20(21):2922-36
40) Proudfoot NJ, et al.  (2002) Integrating mRNA processing with transcription. Cell 108(4):501-12
41) Chedin S, et al.  (1998) The yeast RNA polymerase III transcription machinery: a paradigm for eukaryotic gene activation. Cold Spring Harb Symp Quant Biol 63:381-9
42) Geiduschek EP and Kassavetis GA  (2001) The RNA polymerase III transcription apparatus. J Mol Biol 310(1):1-26
43) Huang Y and Maraia RJ  (2001) Comparison of the RNA polymerase III transcription machinery in Schizosaccharomyces pombe, Saccharomyces cerevisiae and human. Nucleic Acids Res 29(13):2675-90
44) Ciesla M and Boguta M  (2008) Regulation of RNA polymerase III transcription by Maf1 protein. Acta Biochim Pol 55(2):215-25