DIS3/YOL021C Summary Help

Standard Name DIS3 1
Systematic Name YOL021C
Alias RRP44 2 , MTR17 3
Feature Type ORF, Verified
Description Exosome core complex catalytic subunit; has both endonuclease and 3'-5' exonuclease activity; involved in 3'-5' RNA processing and degradation in both the nucleus and the cytoplasm; role in degradation of tRNAs; has similarity to E. coli RNase R and to human DIS3; mutations in Dis3p corresponding to human mutations implicated in multiple myeloma cause phenotypes suggesting impaired exosome function; protein abundance increases in response to DNA replication stress (4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and see Summary Paragraph)
Name Description homolog of S. pombe dis3 (chromosome DISjunction) 1
Chromosomal Location
ChrXV:285426 to 282421 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All DIS3 GO evidence and references
  View Computational GO annotations for DIS3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 5 genes
Resources
Classical genetics
conditional
dominant negative
null
reduction of function
repressible
Large-scale survey
conditional
null
overexpression
reduction of function
Resources
201 total interaction(s) for 59 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 141
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 17
  • Biochemical Activity: 2
  • Co-fractionation: 1
  • Co-purification: 1
  • Reconstituted Complex: 12
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 5
  • Negative Genetic: 9
  • Phenotypic Enhancement: 1
  • Positive Genetic: 3
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,001
Molecular Weight (Da) 113,706
Isoelectric Point (pI) 6.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:285426 to 282421 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
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..3006 285426..282421 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005381
SUMMARY PARAGRAPH for DIS3

The exosome complex possesses 3'-5' exonuclease and endoribonucleolytic activities that are essential for diverse ribonucleolytic processes in both the nucleus and the cytoplasm (2, 14, 15). The nuclear exosome is associated with the TRAMP complex and is involved in RNA catabolic processes including RNA surveillance (16, 17 and references therein), pre-mRNA turnover (18) and the production of mature 3' ends for snoRNAs, snRNAs and rRNAs (14, 19 and references therein). The cytoplasmic exosome is associated with Ski7p and the SKI complex and is involved in RNA catabolic processes that include both the routine turnover of normal mRNA (20) as well as the degradation of aberrant mRNAs (21 and references therein). The 10-subunit core exosome complex (Csl4p, Rrp4p, Rrp40p, Ski6p, Rrp42p, Rrp43p, Rrp45p, Rrp46p, Mtr3p, Dis3p) is the same in both locations, but the nuclear exosome contains an additional subunit (Rrp6p) and two additional accessory factors (Lrp1p, Mpp6p) (15).

Although the exosome was originally described as a "complex of exonucleases," with multiple subunits proposed to have RNase activity (2), later work has shown that this mechanism is unlikely in yeast. With the exception of Ski6p, none of the yeast subunits that show homology to E. coli RNase PH retain the active site residues seen in the bacterial or archael enzymes. Further research has also demonstrated that most, if not all, detectable enzymatic activity resides in the Dis3p and Rrp6p subunits (5, 6).

DIS3 encodes the catalytic subunit of the core exosome complex, and possesses both 3'-5' exonuclease activity and endoribonuclease activity (6, 5, 8, 9, 10). In addition to its nuclease activity, Dis3p is required for recognition of certain exosome substrates (22). Dis3p associates with the exosome through its N-terminus, which mediates interactions with other exosome subunits such as Rrp45p, Rrp43p, and Ski6p (9, 23). Dis3p appears to function in the Ran signaling pathway, as evidenced by its direct binding to the Ran GTPase Gsp1p and its ability to stimulate the guanine nucleotide exchange activity of RCC1, the human homolog of the Ran nucleotide exchange factor Srm1p (1). Mutants null for dis3 are inviable, point mutations in either Dis3p nuclease domain results in slow growth, and conditional and repressible mutants of dis3 accumulate processing intermediates and aberrant forms of various classes of RNAs, including mRNAs and rRNAs (1, 8, 10, 24, 2).

Although Dis3p shares a similar linear arrangement of domains with the bacterial exonuclease RNase II, the tertiary structures of the two enzymes differ and Dis3p is biochemically more like bacterial RNase R (7 and references therein). DIS3 is conserved among eukaryotes, and both fission yeast dis3 and human DIS3 proteins are able to rescue S. cerevisiae dis3 mutant phenotypes (1, 4).

Last updated: 2009-09-09 Contact SGD

References cited on this page View Complete Literature Guide for DIS3
1) Noguchi E, et al.  (1996) Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1. EMBO J 15(20):5595-605
2) Mitchell P, et al.  (1997) The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell 91(4):457-66
3) Smith SB, et al.  (2011) Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant. Yeast 28(11):755-69
4) Shiomi T, et al.  (1998) Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3. J Biochem (Tokyo) 123(5):883-90
5) Liu Q, et al.  (2006) Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 127(6):1223-37
6) Dziembowski A, et al.  (2007) A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol 14(1):15-22
7) Lorentzen E, et al.  (2008) Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. Mol Cell 29(6):717-28
8) Lebreton A, et al.  (2008) Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature 456(7224):993-6
9) Schneider C, et al.  (2009) The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Res 37(4):1127-40
10) Schaeffer D, et al.  (2009) The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol 16(1):56-62
11) 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
12) Gudipati RK, et al.  (2012) Extensive degradation of RNA precursors by the exosome in wild-type cells. Mol Cell 48(3):409-21
13) Tomecki R, et al.  (2014) Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target. Nucleic Acids Res 42(2):1270-90
14) van Hoof A, et al.  (2000) Yeast exosome mutants accumulate 3'-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol Cell Biol 20(2):441-52
15) Synowsky SA, et al.  (2009) Comparative multiplexed mass spectrometric analyses of endogenously expressed yeast nuclear and cytoplasmic exosomes. J Mol Biol 385(4):1300-13
16) Vanacova S, et al.  (2005) A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 3(6):e189
17) LaCava J, et al.  (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121(5):713-24
18) Bousquet-Antonelli C, et al.  (2000) Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell 102(6):765-75
19) Allmang C, et al.  (2000) Degradation of ribosomal RNA precursors by the exosome. Nucleic Acids Res 28(8):1684-91
20) Jacobs JS, et al.  (1998) The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex. EMBO J 17(5):1497-506
21) Schaeffer D, et al.  (2008) Determining in vivo activity of the yeast cytoplasmic exosome. Methods Enzymol 448:227-39
22) Schneider C, et al.  (2007) The exosome subunit Rrp44 plays a direct role in RNA substrate recognition. Mol Cell 27(2):324-31
23) Wang HW, et al.  (2007) Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing. Proc Natl Acad Sci U S A 104(43):16844-9
24) Suzuki N, et al.  (2001) 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 158(2):613-25