MTR4/YJL050W Summary Help

Standard Name MTR4 1
Systematic Name YJL050W
Alias DOB1 2
Feature Type ORF, Verified
Description ATP-dependent 3'-5' RNA helicase of the DExD/H family; involved in nuclear RNA processing and degradation both as a component of TRAMP complex and in TRAMP-independent processes; TRAMP unwinds RNA duplexes, with Mtr4p unwinding activity stimulated by Pap2p/Air2p but not dependent on ongoing polyadenylation; contains an arch domain, with two coiled-coil arms/stalks and a globular fist/KOW domain, which has RNA binding activity and is required for 5.8S rRNA processing (2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Mrna TRansport 12
Chromosomal Location
ChrX:342522 to 345743 | ORF Map | GBrowse
Gene Ontology Annotations All MTR4 GO evidence and references
  View Computational GO annotations for MTR4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
dominant negative
reduction of function
Large-scale survey
reduction of function
151 total interaction(s) for 107 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 60
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 21
  • PCA: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 3
  • Negative Genetic: 52
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 2
  • Positive Genetic: 1
  • Synthetic Growth Defect: 1
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 1,073
Molecular Weight (Da) 122,054
Isoelectric Point (pI) 6.28
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:342522 to 345743 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..3222 342522..345743 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003586

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) (3, 4, 5, and reviewed in 13, 8, and 14). In addition, mutant analysis indicates that TRAMP and the exosome also contribute to the regulation of some mRNAs, such as those encoding histones (15).

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 (16, 17, 18, 19, 20). 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 (21) or as slow growth (4).

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 (22), SKIV2L2 has been identified as the Mtr4p homolog (23, 24, 25) and ZCCHC7 may be the Air1/2p homolog (13).

MTR4 (also known as DOB1) was originally identified in a screen for mutants defective in mRNA transport (12, 1). Mtr4p was later described as a nuclear exosome cofactor (2, 26) and as a component of the TRAMP complex. Mtr4p is an ATP-dependent 3'-5' RNA helicase and has been shown to bind poly(A) RNA directly (6, 7). This enzyme likely functions both in the context of the TRAMP complex as well as in TRAMP-independent exosome processes such as maturation of 5.8S rRNA (8 and references therein).

Last updated: 2009-09-09 Contact SGD

References cited on this page View Complete Literature Guide for MTR4
1) Liang S, et al.  (1996) A DEAD-box-family protein is required for nucleocytoplasmic transport of yeast mRNA. Mol Cell Biol 16(9):5139-46
2) de la Cruz J, et al.  (1998) Dob1p (Mtr4p) is a putative ATP-dependent RNA helicase required for the 3' end formation of 5.8S rRNA in Saccharomyces cerevisiae. EMBO J 17(4):1128-40
3) Vanacova S, et al.  (2005) A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 3(6):e189
4) LaCava J, et al.  (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121(5):713-24
5) 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
6) Wang X, et al.  (2008) Degradation of hypomodified tRNA(iMet) in vivo involves RNA-dependent ATPase activity of the DExH helicase Mtr4p. RNA 14(1):107-16
7) Bernstein J, et al.  (2008) Characterization of the Essential Activities of Saccharomyces cerevisiae Mtr4p, a 3'->5' Helicase Partner of the Nuclear Exosome. J Biol Chem 283(8):4930-42
8) Lebreton A and Seraphin B  (2008) Exosome-mediated quality control: substrate recruitment and molecular activity. Biochim Biophys Acta 1779(9):558-65
9) Jackson RN, et al.  (2010) The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing. EMBO J 29(13):2205-16
10) Weir JR, et al.  (2010) Structural analysis reveals the characteristic features of Mtr4, a DExH helicase involved in nuclear RNA processing and surveillance. Proc Natl Acad Sci U S A 107(27):12139-44
11) Jia H, et al.  (2012) RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex. Proc Natl Acad Sci U S A 109(19):7292-7
12) Kadowaki T, et al.  (1994) Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants. J Cell Biol 126(3):649-59
13) 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
14) Reinisch KM and Wolin SL  (2007) Emerging themes in non-coding RNA quality control. Curr Opin Struct Biol 17(2):209-14
15) 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
16) Houseley J and Tollervey D  (2006) Yeast Trf5p is a nuclear poly(A) polymerase. EMBO Rep 7(2):205-11
17) 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
18) Dez C, et al.  (2007) Roles of the HEAT repeat proteins Utp10 and Utp20 in 40S ribosome maturation. RNA 13(9):1516-27
19) 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
20) San Paolo S, et al.  (2009) Distinct roles of non-canonical poly(A) polymerases in RNA metabolism. PLoS Genet 5(7):e1000555
21) 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
22) 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
23) 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
24) Chen CY, et al.  (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107(4):451-64
25) 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
26) 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