Gene Symbol: DIS3
Description: exosome catalytic subunit DIS3
Alias: MTR17, RRP44, exosome catalytic subunit DIS3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell. 2005;121:713-24 pubmed
    ..We speculate that this function was maintained in eukaryotic nuclei, while cytoplasmic mRNA poly(A) tails acquired different roles in translation. ..
  2. Mitchell P, Petfalski E, Houalla R, Podtelejnikov A, Mann M, Tollervey D. Rrp47p is an exosome-associated protein required for the 3' processing of stable RNAs. Mol Cell Biol. 2003;23:6982-92 pubmed
    ..We propose that Rrp47p functions as a substrate-specific nuclear cofactor for exosome activity in the processing of stable RNAs. ..
  3. Liu J, Bratkowski M, Liu X, Niu C, Ke A, Wang H. Visualization of distinct substrate-recruitment pathways in the yeast exosome by EM. Nat Struct Mol Biol. 2014;21:95-102 pubmed publisher
    The eukaryotic exosome is a multisubunit complex typically composed of a catalytically inactive core and the Rrp44 protein, which contains 3'-to-5' exo- and endo-RNase activities...
  4. Schaeffer D, Tsanova B, Barbas A, Reis F, Dastidar E, Sanchez Rotunno M, et al. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 2009;16:56-62 pubmed publisher
    ..How the exosome accomplishes this is unknown. Rrp44 (also known as Dis3), a member of the RNase II family of enzymes, is the catalytic subunit of the exosome...
  5. Wang H, Wang J, Ding F, Callahan K, Bratkowski M, Butler J, et al. Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing. Proc Natl Acad Sci U S A. 2007;104:16844-9 pubmed
    ..In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3'-to-5' exoribonuclease ..
  6. Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell. 1997;91:457-66 pubmed
    ..8S rRNA. Human Rrp4p is found in a comparably sized complex, and expression of the hRRP4 gene in yeast complements the rrp4-1 mutation. We conclude that the exosome constitutes a highly conserved eukaryotic RNA processing complex. ..
  7. Allmang C, Petfalski E, Podtelejnikov A, Mann M, Tollervey D, Mitchell P. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes Dev. 1999;13:2148-58 pubmed
  8. Gudipati R, Xu Z, Lebreton A, Seraphin B, Steinmetz L, Jacquier A, et al. Extensive degradation of RNA precursors by the exosome in wild-type cells. Mol Cell. 2012;48:409-21 pubmed publisher
  9. Grosshans H, Deinert K, Hurt E, Simos G. Biogenesis of the signal recognition particle (SRP) involves import of SRP proteins into the nucleolus, assembly with the SRP-RNA, and Xpo1p-mediated export. J Cell Biol. 2001;153:745-62 pubmed
    ..Xpo1p, is distinct from mRNA transport, and requires, as evidenced by the nucleolar accumulation of scR1 in a dis3/rrp44 exosome component mutant, an intact scR1 3' end...

More Information


  1. Drazkowska K, Tomecki R, Stodus K, Kowalska K, Czarnocki Cieciura M, Dziembowski A. The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro. Nucleic Acids Res. 2013;41:3845-58 pubmed publisher
    ..The yeast exosome catalytic activity is supplied by the Dis3 (also known as Rrp44) protein, which has both endo- and exoribonucleolytic activities and the nucleus-specific exonuclease Rrp6...
  2. Schneider C, Anderson J, Tollervey D. The exosome subunit Rrp44 plays a direct role in RNA substrate recognition. Mol Cell. 2007;27:324-31 pubmed
    ..We report the functional characterization of the yeast exosome component Rrp44, a member of the RNase II family...
  3. Lee G, Bratkowski M, Ding F, Ke A, Ha T. Elastic coupling between RNA degradation and unwinding by an exoribonuclease. Science. 2012;336:1726-9 pubmed publisher
    b>Rrp44 (Dis3) is a key catalytic subunit of the yeast exosome complex and can processively digest structured RNA one nucleotide at a time in the 3' to 5' direction...
  4. Kadaba S, Wang X, Anderson J. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA. 2006;12:508-21 pubmed
    ..We conclude that an array of RNA polymerase III transcripts are targeted for Trf4p/ Trf5p-dependent polyadenylation and turnover to eliminate mutant and variant forms of normally stable RNAs. ..
  5. Schaeffer D, Reis F, Johnson S, Arraiano C, van Hoof A. The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function. Nucleic Acids Res. 2012;40:9298-307 pubmed publisher
    ..These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated. ..
  6. Wyers F, Rougemaille M, Badis G, Rousselle J, Dufour M, Boulay J, et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell. 2005;121:725-37 pubmed
    ..Our data strongly support the existence of a posttranscriptional quality control mechanism limiting inappropriate expression of genetic information. ..
  7. Bousquet Antonelli C, Presutti C, Tollervey D. Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell. 2000;102:765-75 pubmed
    ..We propose that nuclear pre-mRNA turnover represents a novel step in the regulation of gene expression. ..
  8. Synowsky S, van den Heuvel R, Mohammed S, Pijnappel P, Heck A. Probing genuine strong interactions and post-translational modifications in the heterogeneous yeast exosome protein complex. Mol Cell Proteomics. 2006;5:1581-92 pubmed
    ..The described multiplexed mass spectrometry-based procedure is generic and thus applicable to many different types of cellular molecular machineries even if they are expressed at endogenous levels. ..
  9. Schneider C, Kudla G, Wlotzka W, Tuck A, Tollervey D. Transcriptome-wide analysis of exosome targets. Mol Cell. 2012;48:422-33 pubmed publisher
    ..Here we apply in vivo RNA crosslinking (CRAC) to the nucleases (Rrp44, Rrp6), two structural subunits (Rrp41, Csl4) and a cofactor (Trf4) of the yeast exosome...
  10. Dziembowski A, Lorentzen E, Conti E, Seraphin B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol. 2007;14:15-22 pubmed
    ..nine subunits that form a ring similar to the phosphorolytic bacterial PNPase and archaeal exosome, as well as Dis3. Dis3 is homologous to bacterial RNase II, a hydrolytic enzyme...
  11. Vanacova S, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 2005;3:e189 pubmed
    ..This polyadenylation-mediated RNA surveillance resembles the role of polyadenylation in bacterial RNA turnover. ..
  12. Kadaba S, Krueger A, Trice T, Krecic A, Hinnebusch A, Anderson J. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 2004;18:1227-40 pubmed
    ..The wild-type allele of one suppressor, DIS3/RRP44, encodes a 3'-5' exoribonuclease and a member of the multisubunit exosome complex...
  13. Bonneau F, Basquin J, Ebert J, Lorentzen E, Conti E. The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation. Cell. 2009;139:547-59 pubmed publisher
    ..Here, we investigate how the Rrp44 nuclease functions in the active ten-subunit exosome. The 3...
  14. Lebreton A, Tomecki R, Dziembowski A, Seraphin B. Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature. 2008;456:993-6 pubmed publisher
    ..activity of the yeast exosome core was shown to be mediated by the RNB domain of the eukaryote-specific Dis3 subunit...
  15. Schaeffer D, van Hoof A. Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs. Proc Natl Acad Sci U S A. 2011;108:2366-71 pubmed publisher
    ..Our findings suggest that the nuclease requirements for general and nonstop mRNA decay are different, and describe a molecular function of the core exosome that is not disrupted by inactivating its exonuclease activity. ..
  16. Lorentzen E, Basquin J, Tomecki R, Dziembowski A, Conti E. Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. Mol Cell. 2008;29:717-28 pubmed publisher
    ..It has recently been shown that the RNase activity of the yeast exosome core can be mapped to a single subunit, Rrp44, which processively degrades single-stranded RNAs as well as RNAs containing secondary structures...
  17. Schneider C, Leung E, Brown J, Tollervey D. The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Res. 2009;37:1127-40 pubmed publisher
    Nuclear and cytoplasmic forms of the yeast exosome share 10 components, of which only Rrp44/Dis3 is believed to possess 3' exonuclease activity...
  18. Callahan K, Butler J. Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p. Nucleic Acids Res. 2008;36:6645-55 pubmed publisher
    ..These findings indicate that Rrp6p may carry out some of its critical functions without physical association with the core exosome. ..
  19. Assenholt J, Mouaikel J, Andersen K, Brodersen D, Libri D, Jensen T. Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants. RNA. 2008;14:2305-13 pubmed publisher
    ..Our data show that exonucleolytic attack by the nuclear exosome is needed both for provoking mRNP QC and for its ensuing elimination of faulty RNA. ..
  20. Noguchi E, Hayashi N, Azuma Y, Seki T, Nakamura M, Nakashima N, et al. Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1. EMBO J. 1996;15:5595-605 pubmed
    ..The DIS3 gene is essential for viability and complements S.pombe mutant dis3-54 which is defective in mitosis...
  21. Allmang C, Kufel J, Chanfreau G, Mitchell P, Petfalski E, Tollervey D. Functions of the exosome in rRNA, snoRNA and snRNA synthesis. EMBO J. 1999;18:5399-410 pubmed
    ..We conclude that the exosome is involved in the processing of many RNA substrates and that different components can have distinct functions. ..
  22. Shiomi T, Fukushima K, Suzuki N, Nakashima N, Noguchi E, Nishimoto T. Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3. J Biochem. 1998;123:883-90 pubmed
    Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of Dis3p in S. cerevisiae and S...
  23. Vasiljeva L, Buratowski S. Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II transcripts. Mol Cell. 2006;21:239-48 pubmed
    ..Since Nrd1 is known to bind RNA polymerase II and be important for sn/snoRNA 3' end processing, Nrd1 may link transcription and RNA 3' end formation with surveillance by the exosome. ..
  24. Synowsky S, van Wijk M, Raijmakers R, Heck A. Comparative multiplexed mass spectrometric analyses of endogenously expressed yeast nuclear and cytoplasmic exosomes. J Mol Biol. 2009;385:1300-13 pubmed publisher
    ..We show that the nuclear exosome selectively copurifies with the alpha/beta importin heterodimer, which is known to be involved in the transport of proteins across the nuclear membrane. ..
  25. Delan Forino C, Schneider C, Tollervey D. Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex. PLoS Genet. 2017;13:e1006699 pubmed publisher
    ..threaded through the central channel of the exosome or more directly access the active sites of the ribonucleases Rrp44 and Rrp6, but it was unclear how many substrates follow each pathway in vivo...
  26. Wasmuth E, Lima C. The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome. Nucleic Acids Res. 2017;45:846-860 pubmed publisher
    ..non-catalytic donut-shaped core includes 9 subunits that associate with the 3' to 5' exoribonucleases Rrp6, and Rrp44/Dis3, a subunit that also catalyzes endoribonuclease activity...
  27. Paul B, Montpetit B. Altered RNA processing and export lead to retention of mRNAs near transcription sites and nuclear pore complexes or within the nucleolus. Mol Biol Cell. 2016;27:2742-56 pubmed publisher
    ..These data show that alterations to various nuclear processes lead to the retention of mRNAs at discrete locations within the nucleus. ..
  28. Kowalinski E, Kögel A, Ebert J, Reichelt P, Stegmann E, Habermann B, et al. Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex. Mol Cell. 2016;63:125-34 pubmed publisher
    ..Knowledge of the interacting residues in the yeast complexes allowed us to identify a splice variant of human HBS1-Like as a Ski7-like exosome-binding protein, revealing the evolutionary conservation of this cytoplasmic cofactor. ..
  29. Kim K, Heo D, Kim I, Suh J, Kim M. Exosome Cofactors Connect Transcription Termination to RNA Processing by Guiding Terminated Transcripts to the Appropriate Exonuclease within the Nuclear Exosome. J Biol Chem. 2016;291:13229-42 pubmed publisher
    ..Importantly, Mpp6 promotes the processing of Nrd1-terminated transcripts preferentially by Dis3, whereas Trf4 leads to Rrp6-dependent processing...
  30. Heo D, Yoo I, Kong J, Lidschreiber M, Mayer A, Choi B, et al. The RNA polymerase II C-terminal domain-interacting domain of yeast Nrd1 contributes to the choice of termination pathway and couples to RNA processing by the nuclear exosome. J Biol Chem. 2013;288:36676-90 pubmed publisher
    ..Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome. ..
  31. Luz J, Tavares J, Gonzales F, Santos M, Oliveira C. Analysis of the Saccharomyces cerevisiae exosome architecture and of the RNA binding activity of Rrp40p. Biochimie. 2007;89:686-91 pubmed
    ..We also show evidence that Rrp40p can bind RNA in vitro, as predicted by sequence analysis. ..
  32. Falk S, Bonneau F, Ebert J, Kögel A, Conti E. Mpp6 Incorporation in the Nuclear Exosome Contributes to RNA Channeling through the Mtr4 Helicase. Cell Rep. 2017;20:2279-2286 pubmed publisher
    ..In the yeast nucleus, the ubiquitous 10-subunit exosome core complex (Exo-9-Rrp44) functions with four conserved cofactors (Rrp6, Rrp47, Mtr4, and Mpp6)...
  33. Taverner T, Hernandez H, Sharon M, Ruotolo B, Matak Vinkovic D, Devos D, et al. Subunit architecture of intact protein complexes from mass spectrometry and homology modeling. Acc Chem Res. 2008;41:617-27 pubmed publisher
    ..Overall therefore this mass spectrometry and homology modeling approach has given significant insight into the structure of two previously intractable protein complexes and as such has broad application in structural biology. ..
  34. Tomecki R, Drazkowska K, Kucinski I, Stodus K, Szczesny R, Gruchota J, et al. Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target. Nucleic Acids Res. 2014;42:1270-90 pubmed publisher
    ..Yeast harboring corresponding mutations in DIS3 show growth inhibition and changes in nuclear RNA metabolism typical for exosome dysfunction...
  35. Abruzzi K, Denome S, Olsen J, Assenholt J, Haaning L, Jensen T, et al. A novel plasmid-based microarray screen identifies suppressors of rrp6Delta in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:1044-55 pubmed
    ..Microarray analyses of gene expression in rrp6Delta strains and a number of suppressor strains support this hypothesis. ..
  36. Liu J, Niu C, Wu Y, Tan D, Wang Y, Ye M, et al. CryoEM structure of yeast cytoplasmic exosome complex. Cell Res. 2016;26:822-37 pubmed publisher
    ..Further structural analysis of exosomes with RNA substrates harboring 3' overhangs of different length suggests a switch mechanism of RNA-induced exosome activation in the through-core pathway of RNA processing. ..
  37. Frenk S, Oxley D, Houseley J. The nuclear exosome is active and important during budding yeast meiosis. PLoS ONE. 2014;9:e107648 pubmed publisher
    ..Together, our results show that the nuclear exosome remains active in meiosis and has an important role in facilitating meiotic recombination. ..
  38. Azzouz N, Panasenko O, Colau G, Collart M. The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome. PLoS ONE. 2009;4:e6760 pubmed publisher
    ..Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation. ..
  39. Leung E, Schneider C, Yan F, Mohi El Din H, Kudla G, Tuck A, et al. Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery. Nucleic Acids Res. 2014;42:10698-710 pubmed publisher
    ..We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, potentially facilitating the decision between these alternative fates. ..
  40. Ramírez Garrastacho M, Esteban R. Yeast RNA viruses as indicators of exosome activity: human exosome hCsl4p participates in RNA degradation in Saccharomyces cerevisiae'. Yeast. 2011;28:821-32 pubmed publisher
  41. Smith S, Kiss D, Turk E, Tartakoff A, Andrulis E. Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant. Yeast. 2011;28:755-69 pubmed publisher
    ..Here, in a genetic, cell biological and transcriptomic analysis, we examined the role of Dis3, an essential polypeptide with endo- and 3'?5' exo-ribonuclease activity, in cell cycle progression...
  42. Cole S, LaRiviere F, Merrikh C, Moore M. A convergence of rRNA and mRNA quality control pathways revealed by mechanistic analysis of nonfunctional rRNA decay. Mol Cell. 2009;34:440-50 pubmed publisher
    ..We propose that 18S NRD and NGD are different observable outcomes of the same initiating event: a ribosome stalled inappropriately at a sense codon during translation elongation. ..
  43. Suzuki N, Noguchi E, Nakashima N, Oki M, Ohba T, Tartakoff A, et al. The Saccharomyces cerevisiae small GTPase, Gsp1p/Ran, is involved in 3' processing of 7S-to-5.8S rRNA and in degradation of the excised 5'-A0 fragment of 35S pre-rRNA, both of which are carried out by the exosome. Genetics. 2001;158:613-25 pubmed
    ..between the exosome and the RanGTPase cycle, a series of temperature-sensitive Saccharomyces cerevisiae dis3 mutants were isolated and their 5.8S rRNA processing was compared with processing in strains with mutations in a S...
  44. Colin J, Candelli T, Porrúa O, Boulay J, Zhu C, Lacroute F, et al. Roadblock termination by reb1p restricts cryptic and readthrough transcription. Mol Cell. 2014;56:667-80 pubmed publisher
    ..This work demonstrates the importance of roadblock termination for controlling pervasive transcription and preventing transcription through gene regulatory regions. ..
  45. Tsanova B, Spatrick P, Jacobson A, van Hoof A. The RNA exosome affects iron response and sensitivity to oxidative stress. RNA. 2014;20:1057-67 pubmed publisher
    ..We show that inactivating the exoribonuclease active site of Rrp44 up-regulates the iron uptake regulon...
  46. Zinder J, Wasmuth E, Lima C. Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3. Mol Cell. 2016;64:734-745 pubmed publisher
    ..The nuclear RNA exosome includes a 9-subunit non-catalytic core that binds Rrp44 (Dis3) and Rrp6 subunits to modulate their processive and distributive 3'-to-5' exoribonuclease activities, ..