TRF5/YNL299W Summary Help

Standard Name TRF5 1
Systematic Name YNL299W
Feature Type ORF, Verified
Description Non-canonical poly(A) polymerase; involved in nuclear RNA degradation as a component of the TRAMP complex; catalyzes polyadenylation of hypomodified tRNAs, and snoRNA and rRNA precursors; overlapping but non-redundant functions with Pap2p; TRF5 has a paralog, PAP2, that arose from the whole genome duplication (2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Topoisomerase one-Related Function 1
Chromosomal Location
ChrXIV:66517 to 68445 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All TRF5 GO evidence and references
  View Computational GO annotations for TRF5
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 1 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
Resources
110 total interaction(s) for 80 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 12
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 3
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 50
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 3
  • Positive Genetic: 8
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 9
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 642
Molecular Weight (Da) 74,179
Isoelectric Point (pI) 7.02
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:66517 to 68445 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2005-11-07 | Sequence: 2005-11-03
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1929 66517..68445 2005-11-07 2005-11-03
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 SGDIDS000005243
SUMMARY PARAGRAPH for TRF5

The TRAMP complex is a nuclear complex that functions in RNA processing, degradation and surveillance. The TRAMP (TRf4/5p, Air1/2p, Mtr4p Polyadenylation) complex polyadenylates a variety of nuclear RNAs, thereby targeting these RNAs for processing or degradation by the exosome. Characterized substrates of the TRAMP complex include aberrant and hypomodified tRNAs; aberrant and precursor snoRNAs, snRNAs and rRNAs; and cryptic unstable transcripts (CUTs) (2, 3, 8, and reviewed in 9, 10, and 11). In addition, mutant analysis indicates that TRAMP and the exosome also contribute to the regulation of some mRNAs, such as those encoding histones (12).

The TRAMP complex contains three proteins: a non-canonical poly(A) polymerase (either Pap2p (aka Trf4p) or Trf5p), a DExD/H family RNA helicase (Mtr4p) and a zinc knuckle domain protein (either Air1p or Air2p). Analysis of PAP2 and TRF5 mutants show that these genes have overlapping but not redundant functions, and the terms "TRAMP4" and "TRAMP5" are sometimes used to distinguish complexes containing Pap2p from those containing Trf5p (7, 6, 13, 14, 15). AIR1 and AIR2 appear to be functionally redundant, as deletion of either gene does not cause a detectable phenotype, but the air1air2 double deletion is variously described as synthetically lethal (16) or as slow growth (3).

Although the TRAMP complex has not yet been isolated in humans, the human genome does contain sequences homologous to all three yeast TRAMP components. TRF4-1 and TRF4-2 have been identified as Pap2p and Trf5p homologs (17), SKIV2L2 has been identified as the Mtr4p homolog (18, 19, 20) and ZCCHC7 may be the Air1/2p homolog (9).

The TRAMP component Pap2p (more commonly called Trf4p) is a poly(A) polymerase that was originally isolated in a screen for mutants that were rescued by overexpression of DNA topoisomerase I (TOP1) (21). Pap2p was initially characterized as a DNA polymerase and was thought to be involved in sister-chromatid cohesion (22, 23, 24), functions that were also ascribed to poly(A) polymerase Trf5p, based on homology (1). However, later work established that these early conclusions were incorrect: Pap2p is not a DNA polymerase and is not required for sister chromatid cohesion (25, 4, 26). More recently, Pap2p has been reported to also have 5'-deoxyribose-5-phosphate lyase activity, and both Pap2p and Trf5p have been implicated in base excision repair (27).

Last updated: 2009-09-09 Contact SGD

References cited on this page View Complete Literature Guide for TRF5
1) Castano IB, et al.  (1996) A novel family of TRF (DNA topoisomerase I-related function) genes required for proper nuclear segregation. Nucleic Acids Res 24(12):2404-10
2) Vanacova S, et al.  (2005) A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 3(6):e189
3) LaCava J, et al.  (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121(5):713-24
4) Haracska L, et al.  (2005) Trf4 and Trf5 proteins of Saccharomyces cerevisiae exhibit poly(A) RNA polymerase activity but no DNA polymerase activity. Mol Cell Biol 25(22):10183-9
5) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
6) Egecioglu DE, et al.  (2006) Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA 12(1):26-32
7) Houseley J and Tollervey D  (2006) Yeast Trf5p is a nuclear poly(A) polymerase. EMBO Rep 7(2):205-11
8) Wyers F, et al.  (2005) Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121(5):725-37
9) Houseley J and Tollervey D  (2008) The nuclear RNA surveillance machinery: The link between ncRNAs and genome structure in budding yeast? Biochim Biophys Acta 1779(4):239-46
10) Lebreton A and Seraphin B  (2008) Exosome-mediated quality control: substrate recruitment and molecular activity. Biochim Biophys Acta 1779(9):558-65
11) Reinisch KM and Wolin SL  (2007) Emerging themes in non-coding RNA quality control. Curr Opin Struct Biol 17(2):209-14
12) Reis CC and Campbell JL  (2007) Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae. Genetics 175(3):993-1010
13) Dez C, et al.  (2007) Roles of the HEAT repeat proteins Utp10 and Utp20 in 40S ribosome maturation. RNA 13(9):1516-27
14) Kadaba S, et al.  (2006) Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA 12(3):508-21
15) San Paolo S, et al.  (2009) Distinct roles of non-canonical poly(A) polymerases in RNA metabolism. PLoS Genet 5(7):e1000555
16) Inoue K, et al.  (2000) Novel RING finger proteins, Air1p and Air2p, interact with Hmt1p and inhibit the arginine methylation of Npl3p. J Biol Chem 275(42):32793-9
17) Walowsky C, et al.  (1999) The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. J Biol Chem 274(11):7302-8
18) Schilders G, et al.  (2007) C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic Acids Res 35(8):2564-72
19) Chen CY, et al.  (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107(4):451-64
20) Nagahama M, et al.  (2006) The AAA-ATPase NVL2 is a component of pre-ribosomal particles that interacts with the DExD/H-box RNA helicase DOB1. Biochem Biophys Res Commun 346(3):1075-82
21) Sadoff BU, et al.  (1995) Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics 141(2):465-79
22) Wang Z, et al.  (2000) Pol kappa: A DNA polymerase required for sister chromatid cohesion. Science 289(5480):774-9
23) Castano IB, et al.  (1996) Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae. Genes Dev 10(20):2564-76
24) Wang Z, et al.  (2002) Structure/function analysis of the Saccharomyces cerevisiae Trf4/Pol sigma DNA polymerase. Genetics 160(2):381-91
25) Petronczki M, et al.  (2004) Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II. J Cell Sci 117(Pt 16):3547-59
26) Saitoh S, et al.  (2002) Cid13 is a cytoplasmic poly(A) polymerase that regulates ribonucleotide reductase mRNA. Cell 109(5):563-73
27) Gellon L, et al.  (2008) Intrinsic 5'-deoxyribose-5-phosphate lyase activity in Saccharomyces cerevisiae Trf4 protein with a possible role in base excision DNA repair. DNA Repair (Amst) 7(2):187-98