PRP19/YLL036C Summary Help

Standard Name PRP19 1, 2
Systematic Name YLL036C
Alias PSO4 3
Feature Type ORF, Verified
Description Splicing factor associated with the spliceosome; contains a U-box, a motif found in a class of ubiquitin ligases, and a WD40 domain; relocalizes to the cytosol in response to hypoxia (4, 5, 6 and see Summary Paragraph)
Name Description Pre-RNA Processing 1
Chromosomal Location
ChrXII:68256 to 66745 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All PRP19 GO evidence and references
  View Computational GO annotations for PRP19
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 76 genes
Classical genetics
Large-scale survey
382 total interaction(s) for 157 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 143
  • Affinity Capture-Western: 55
  • Biochemical Activity: 1
  • Co-purification: 103
  • Far Western: 6
  • Protein-peptide: 1
  • Reconstituted Complex: 6
  • Two-hybrid: 24

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 20
  • Phenotypic Enhancement: 2
  • Positive Genetic: 12
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 5
  • Synthetic Rescue: 2

Expression Summary
Length (a.a.) 503
Molecular Weight (Da) 56,569
Isoelectric Point (pI) 4.87
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:68256 to 66745 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1512 68256..66745 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003959

About the NineTeen Complex

The nineteen complex (for prp NineTeen associated Complex and also referred to as the NTC) is a non-snRNA containing protein complex involved in splicing of nuclear RNAs via the spliceosome. It was originally isolated as a complex containing Prp19p and at least eight other proteins that complemented the splicing defect of extracts from prp19 mutant cells (7). Subsequent work has identified the genes encoding the additional members of the complex: NTC20 (8), SNT309 (9), ISY1 (8), SYF2 (10, 11), CWC2 (12), PRP46 (12), CLF1 (11, 12), CEF1 (13), and SYF1 (11, 12). The complex appears to be conserved as mammalian cells contain a functional equivalent called the Prp19/CDC5 complex composed of a similar, though not identical, set of proteins (14). The nineteen complex associates with the assembling splicesosome during or after the dissociation of the U4 snRNA, stabilizes the U5 and U6 snRNAs in the activated spliceosomal complex that is catalytic for the first step of splicing, and remains through the second step of splicing (15, 16). Following disassembly of the spliceosome, members of the nineteen complex have been found in association with the excised intron (17, 18).

The nineteen complex also appears to be involved in control of fidelity and efficiency of splicing. Mutations in isy1 suppress the relaxed fidelity of recognition of the conserved branchpoint sequence conferred by mutations in prp16, an ATP-dependent RNA helicase required for the second step of splicing, and an isy1 null mutation decreases accuracy of 3'-splice site usage (19). In addition, cells with mutations in prp45, a protein found in association with NineTeen complex members, are defective in splicing of introns with non-canonical sequences at the branchpoint or the 5' or 3' splice sites (20). Splicing efficiency of various transcripts is differentially affected by mutations in spliceosomal components, such as PRP19, suggesting that the spliceosome can distinguish between individual transcripts and possibly use these differences to specifically regulate gene expression via control of splicing (21). Interestingly, the Drosophila crooked neck protein (the homolog of CLF1) regulates glial cell differentiation by facilitating the splicing of specific target genes (22).

Mutational and genetic analysis of several nineteen complex subunits has suggested involvement in other cellular processes in addition to splicing, such as cell cycle regulation, cytoskeletal structure, DNA repair, and vesicular transport (23, 18, 24, 10, 25, 25 26). In most cases it appears that the primary defect is in splicing and the other defects are the result of failure to remove an intron from the transcript of a gene involved in that process. However Clf1p, and possibly also Prp19p, may have other direct roles in addition to splicing.

About PRP19

Prp19p is an essential protein and a core component of the nineteen complex that is essential for spliceosomal splicing of nuclear mRNAs (1, 2). It tetramerizes via a central coiled-coil domain and thus forms a central structural element of the nineteen complex to which several other proteins, such as Cef1p, Snt309p, and Cwc2p, bind (5). The four C-terminal WD40 segments form globular domains that may form a typical beta-propeller structure held together by a central stalk formed by the coiled-coil domains (5). The amino terminus contains a U-box domain that has E3 ubiquitin ligase activity in vitro (4). Mutations which disrupt tetramer formation or the E3 ubiquitin ligase activity of Prp19p are both lethal (5, 4).

Originally identified in a screen for mutations conferring sensitivity to DNA damaging agents, it has long been proposed that Prp19p plays a direct role in repair of DNA damage, both in yeast and in other species (27, 28, and references therein). However, in S. cerevisiae, decreased efficiency of splicing of intron-containing genes involved in recombination (MEI4, MER2/REC107, REC114, and DMC1), repair (e.g. MMS2, RFA2, RAD14, and KIN28), cell cycle or chromosome segregation (e.g. UBC9, GLC7, HOP2, CIN2, and MOB1) appears to be a sufficient explanation for the cell cycle and DNA repair defects of prp19 mutant cells, though a role for Prp19p as a nuclear scaffold protein remains possible (29).

PRP19 is conserved across many species, with homologs found in H. sapiens, M. musculus, C. elegans, D. melanogaster, A. thaliana, S. pombe, and even P. falciparum (30, 31). As a member of the Prp19/CDC5 complex, the role of Prp19p in splicing is conserved in mammalian cells (14). The human protein (called hPso4) localizes to the nuclear matrix (30), interacts with a regulatory subunit of the 26S proteasome (32; 31), and may have roles in replicative lifespan (33), DNA repair, and apoptosis (34).

Last updated: 2009-12-11 Contact SGD

References cited on this page View Complete Literature Guide for PRP19
1) Vijayraghavan U, et al.  (1989) Isolation and characterization of pre-mRNA splicing mutants of Saccharomyces cerevisiae. Genes Dev 3(8):1206-16
2) Cheng SC, et al.  (1993) PRP19: a novel spliceosomal component. Mol Cell Biol 13(3):1876-82
3) Henriques JA, et al.  (1989) PSO4: a novel gene involved in error-prone repair in Saccharomyces cerevisiae. Mutat Res 218(2):111-24
4) Ohi MD, et al.  (2003) Structural insights into the U-box, a domain associated with multi-ubiquitination. Nat Struct Biol 10(4):250-5
5) Ohi MD, et al.  (2005) Structural and functional analysis of essential pre-mRNA splicing factor Prp19p. Mol Cell Biol 25(1):451-60
6) Ghosh Dastidar R, et al.  (2012) The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell Biosci 2(1):30
7) Tarn WY, et al.  (1994) Functional association of essential splicing factor(s) with PRP19 in a protein complex. EMBO J 13(10):2421-31
8) Chen CH, et al.  (2001) Identification and characterization of two novel components of the Prp19p-associated complex, Ntc30p and Ntc20p. J Biol Chem 276(1):488-94
9) Chen HR, et al.  (1998) Snt309p, a component of the Prp19p-associated complex that interacts with Prp19p and associates with the spliceosome simultaneously with or immediately after dissociation of U4 in the same manner as Prp19p. Mol Cell Biol 18(4):2196-204
10) Ben-Yehuda S, et al.  (2000) Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae. Genetics 156(4):1503-17
11) Chen CH, et al.  (2002) Functional and physical interactions between components of the Prp19p-associated complex. Nucleic Acids Res 30(4):1029-37
12) Ohi MD and Gould KL  (2002) Characterization of interactions among the Cef1p-Prp19p-associated splicing complex. RNA 8(6):798-815
13) Tsai WY, et al.  (1999) Cef1p is a component of the Prp19p-associated complex and essential for pre-mRNA splicing. J Biol Chem 274(14):9455-62
14) Wahl MC, et al.  (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136(4):701-18
15) Chan SP, et al.  (2003) The Prp19p-associated complex in spliceosome activation. Science 302(5643):279-82
16) Chan SP and Cheng SC  (2005) The Prp19-associated complex is required for specifying interactions of U5 and U6 with pre-mRNA during spliceosome activation. J Biol Chem 280(35):31190-9
17) Dix I, et al.  (1999) The identification and characterization of a novel splicing protein, Isy1p, of Saccharomyces cerevisiae. RNA 5(3):360-8
18) Russell CS, et al.  (2000) Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae. RNA 6(11):1565-72
19) Villa T and Guthrie C  (2005) The Isy1p component of the NineTeen complex interacts with the ATPase Prp16p to regulate the fidelity of pre-mRNA splicing. Genes Dev 19(16):1894-904
20) Gahura O, et al.  (2009) Prp45 affects Prp22 partition in spliceosomal complexes and splicing efficiency of non-consensus substrates. J Cell Biochem 106(1):139-51
21) Pleiss JA, et al.  (2007) Transcript specificity in yeast pre-mRNA splicing revealed by mutations in core spliceosomal components. PLoS Biol 5(4):e90
22) Edenfeld G, et al.  (2006) The splicing factor crooked neck associates with the RNA-binding protein HOW to control glial cell maturation in Drosophila. Neuron 52(6):969-80
23) Vincent K, et al.  (2003) Genetic interactions with CLF1 identify additional pre-mRNA splicing factors and a link between activators of yeast vesicular transport and splicing. Genetics 164(3):895-907
24) Ohi R, et al.  (1998) Myb-related Schizosaccharomyces pombe cdc5p is structurally and functionally conserved in eukaryotes. Mol Cell Biol 18(7):4097-108
25) Dahan O and Kupiec M  (2002) Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint. Nucleic Acids Res 30(20):4361-70
26) Burns CG, et al.  (2002) Removal of a single alpha-tubulin gene intron suppresses cell cycle arrest phenotypes of splicing factor mutations in Saccharomyces cerevisiae. Mol Cell Biol 22(3):801-15
27) Brendel M, et al.  (2003) Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae. Mutat Res 544(2-3):179-93
28) Lu X and Legerski RJ  (2007) The Prp19/Pso4 core complex undergoes ubiquitylation and structural alterations in response to DNA damage. Biochem Biophys Res Commun 354(4):968-74
29) Revers LF, et al.  (2002) Thermoconditional modulation of the pleiotropic sensitivity phenotype by the Saccharomyces cerevisiae PRP19 mutant allele pso4-1. Nucleic Acids Res 30(22):4993-5003
30) Gotzmann J, et al.  (2000) hNMP 200: a novel human common nuclear matrix protein combining structural and regulatory functions. Exp Cell Res 261(1):166-79
31) Sihn CR, et al.  (2007) Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome. Biochem Biophys Res Commun 356(1):175-80
32) Loscher M, et al.  (2005) Interaction of U-box E3 ligase SNEV with PSMB4, the beta7 subunit of the 20 S proteasome. Biochem J 388(Pt 2):593-603
33) Grillari J, et al.  (2005) SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. Nucleic Acids Res 33(21):6868-83
34) Mahajan KN and Mitchell BS  (2003) Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase. Proc Natl Acad Sci U S A 100(19):10746-51