Gene Symbol: MTR4
Description: ATP-dependent RNA helicase MTR4
Alias: DOB1, ATP-dependent RNA helicase MTR4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Liang S, Hitomi M, Hu Y, Liu Y, Tartakoff A. A DEAD-box-family protein is required for nucleocytoplasmic transport of yeast mRNA. Mol Cell Biol. 1996;16:5139-46 pubmed
    ..Corresponding dense material is also seen by electron microscopy. MTR4 is essential for growth and encodes a novel nuclear protein with a size of approximately 120 kDa...
  2. Jackson R, Klauer A, Hintze B, Robinson H, van Hoof A, Johnson S. The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing. EMBO J. 2010;29:2205-16 pubmed publisher
    The essential RNA helicase, Mtr4, performs a critical role in RNA processing and degradation as an activator of the nuclear exosome...
  3. Houseley J, Tollervey D. Yeast Trf5p is a nuclear poly(A) polymerase. EMBO Rep. 2006;7:205-11 pubmed
    ..Trf5p co-purified with Mtr4p and Air1p, indicating that it forms a complex, designated TRAMP5, that has functions that partially overlap with the TRAMP complex. ..
  4. 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. ..
  5. Dez C, Houseley J, Tollervey D. Surveillance of nuclear-restricted pre-ribosomes within a subnucleolar region of Saccharomyces cerevisiae. EMBO J. 2006;25:1534-46 pubmed
    ..Localization of pre-ribosomes to this focus was lost in sda1-2 strains lacking Trf4p or Rrp6p. We designate this nucleolar focus the No-body and propose that it represents a site of pre-ribosome surveillance. ..
  6. De la Cruz J, Kressler D, Tollervey D, Linder P. Dob1p (Mtr4p) is a putative ATP-dependent RNA helicase required for the 3' end formation of 5.8S rRNA in Saccharomyces cerevisiae. EMBO J. 1998;17:1128-40 pubmed
    The temperature-sensitive mutation, dob1-1, was identified in a screen for dependence on overexpression of the yeast translation initiation factor eIF4B (Tif3p). Dob1p is an essential putative ATP-dependent RNA helicase...
  7. 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. ..
  8. Weir J, Bonneau F, Hentschel J, Conti E. 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. 2010;107:12139-44 pubmed publisher
    b>Mtr4 is a conserved RNA helicase that functions together with the nuclear exosome. It participates in the processing of structured RNAs, including the maturation of 5.8S ribosomal RNA (rRNA)...
  9. Jia H, Wang X, Liu F, Guenther U, Srinivasan S, Anderson J, et al. The RNA helicase Mtr4p modulates polyadenylation in the TRAMP complex. Cell. 2011;145:890-901 pubmed publisher
    ..Our data establish Mtr4p as a critical regulator of polyadenylation by TRAMP and reveal that an RNA helicase can control the activity of another enzyme in a highly complex fashion and in response to features in RNA. ..

More Information


  1. Holub P, Lalakova J, Cerná H, Pasulka J, Sarazova M, Hrazdilova K, et al. Air2p is critical for the assembly and RNA-binding of the TRAMP complex and the KOW domain of Mtr4p is crucial for exosome activation. Nucleic Acids Res. 2012;40:5679-93 pubmed publisher
    ..Finally, we uncover the RNA binding part of the Mtr4p arch, the KOW domain, as the essential component for TRAMP-mediated exosome activation. ..
  2. Bernstein J, Patterson D, Wilson G, Toth E. Characterization of the essential activities of Saccharomyces cerevisiae Mtr4p, a 3'->5' helicase partner of the nuclear exosome. J Biol Chem. 2008;283:4930-42 pubmed
    ..This binding exhibits apparent cooperativity and different dynamic behavior from binding to the random single-stranded RNA. This unique binding mode might be employed primarily for degradation. ..
  3. Bernstein J, Ballin J, Patterson D, Wilson G, Toth E. Unique properties of the Mtr4p-poly(A) complex suggest a role in substrate targeting. Biochemistry. 2010;49:10357-70 pubmed publisher
    ..These findings indicate that the Mtr4p-poly(A) complex is unique and ideally suited for targeting key substrates to the exosome. ..
  4. Klauer A, van Hoof A. Genetic interactions suggest multiple distinct roles of the arch and core helicase domains of Mtr4 in Rrp6 and exosome function. Nucleic Acids Res. 2013;41:533-41 pubmed publisher
    ..The activity and specificity of the RNA exosome is thought to be controlled by a number of cofactors. Mtr4 is an essential RNA-dependent adenosine triphosphatase that is required for all of the nuclear functions of the RNA ..
  5. 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. ..
  6. 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. ..
  7. Rougemaille M, Gudipati R, Olesen J, Thomsen R, Seraphin B, Libri D, et al. Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants. EMBO J. 2007;26:2317-26 pubmed
  8. Fasken M, Leung S, Banerjee A, Kodani M, Chavez R, Bowman E, et al. Air1 zinc knuckles 4 and 5 and a conserved IWRXY motif are critical for the function and integrity of the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) RNA quality control complex. J Biol Chem. 2011;286:37429-45 pubmed publisher
    ..The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S...
  9. van Hoof A, Lennertz P, Parker R. Yeast exosome mutants accumulate 3'-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol Cell Biol. 2000;20:441-52 pubmed
    ..and Mtr4p, whereas mRNA degradation by the exosome required Ski2p and was not affected by mutations in RRP6 or MTR4. This finding suggests that the cytoplasmic and nuclear forms of the exosome represent two functionally different ..
  10. Wang X, Jia H, Jankowsky E, Anderson J. Degradation of hypomodified tRNA(iMet) in vivo involves RNA-dependent ATPase activity of the DExH helicase Mtr4p. RNA. 2008;14:107-16 pubmed
    ..Here we show through a genetic analysis that MTR4 is required for degradation but not for polyadenylation of hypomodified tRNA(iMet)...
  11. Jia H, Wang X, Anderson J, Jankowsky E. RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex. Proc Natl Acad Sci U S A. 2012;109:7292-7 pubmed publisher
    Many RNA-processing events in the cell nucleus involve the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex, which contains the poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and the RNA helicase Mtr4p...
  12. Callahan K, Butler J. TRAMP complex enhances RNA degradation by the nuclear exosome component Rrp6. J Biol Chem. 2010;285:3540-7 pubmed publisher
    ..Rrp6 activity by TRAMP, suggesting that neither the poly(A) polymerase activity of Trf4 nor the helicase activity of Mtr4 plays a role in the enhancement. These findings identify TRAMP as an exosome-independent enhancer of Rrp6 activity.
  13. 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. ..
  14. Hilleren P, McCarthy T, Rosbash M, Parker R, Jensen T. Quality control of mRNA 3'-end processing is linked to the nuclear exosome. Nature. 2001;413:538-42 pubmed
    ..In exosome mutants, hypo- as well as hyperadenylated mRNAs are released and translated. These observations suggest that the exosome contributes to a checkpoint that monitors proper 3'-end formation of mRNA. ..
  15. Falk S, Weir J, Hentschel J, Reichelt P, Bonneau F, Conti E. The molecular architecture of the TRAMP complex reveals the organization and interplay of its two catalytic activities. Mol Cell. 2014;55:856-867 pubmed publisher associated with the nuclear exosome and consists of a poly(A)polymerase subcomplex (Trf4-Air2) and a helicase (Mtr4). We found that N-terminal low-complexity regions of Trf4 and Air2 bind Mtr4 in a cooperative manner. The 2...
  16. 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. ..
  17. Taylor L, Jackson R, Rexhepaj M, King A, Lott L, van Hoof A, et al. The Mtr4 ratchet helix and arch domain both function to promote RNA unwinding. Nucleic Acids Res. 2014;42:13861-72 pubmed publisher
    b>Mtr4 is a conserved Ski2-like RNA helicase and a subunit of the TRAMP complex that activates exosome-mediated 3'-5' turnover in nuclear RNA surveillance and processing pathways...
  18. 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
    ..cDNA) in growing cells to identify transcriptome-wide interactions of RNAs with the major nuclear exosome-cofactor Mtr4 and with individual exosome subunits (Rrp6, Csl4, Rrp41 and Rrp44) along the threaded RNA path...
  19. Falk S, Tants J, Basquin J, Thoms M, Hurt E, Sattler M, et al. Structural insights into the interaction of the nuclear exosome helicase Mtr4 with the preribosomal protein Nop53. RNA. 2017;23:1780-1787 pubmed publisher
    The nuclear exosome and the associated RNA helicase Mtr4 participate in the processing of several ribonucleoprotein particles (RNP), including the maturation of the large ribosomal subunit (60S). S...
  20. González Aguilera C, Tous C, Gómez González B, Huertas P, Luna R, Aguilera A. The THP1-SAC3-SUS1-CDC31 complex works in transcription elongation-mRNA export preventing RNA-mediated genome instability. Mol Biol Cell. 2008;19:4310-8 pubmed publisher
  21. Yang C, Hindes A, Hultman K, Johnson S. Mutations in gfpt1 and skiv2l2 cause distinct stage-specific defects in larval melanocyte regeneration in zebrafish. PLoS Genet. 2007;3:e88 pubmed
  22. 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
    ..Neither 5.8S rRNA intermediates nor 5'-A0 fragments were observed in mutants defective in the nucleocytoplasmic transport, indicating that Gsp1p regulates rRNA processing through Dis3p, independent of nucleocytoplasmic transport. ..
  23. Li Y, Burclaff J, Anderson J. Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNAiMet Turnover in Saccharomyces cerevisiae and Mtr4p Enzymatic Activities In Vitro. PLoS ONE. 2016;11:e0148090 pubmed publisher
    ..The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core...
  24. Losh J, King A, Bakelar J, Taylor L, Loomis J, Rosenzweig J, et al. Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing. Nucleic Acids Res. 2015;43:1848-58 pubmed
    ..Four of these exosome cofactors have enzymatic activity, namely, the nuclear RNA-dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical poly(A) polymerases, Trf4 and Trf5...
  25. 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
    ..Recognition of hypomodified tRNA(i)(Met) by Rrp44 is genetically separable from its catalytic activity on other substrates, with the mutations mapping to distinct regions of the protein. ..
  26. Roth K, Byam J, Fang F, Butler J. Regulation of NAB2 mRNA 3'-end formation requires the core exosome and the Trf4p component of the TRAMP complex. RNA. 2009;15:1045-58 pubmed publisher
    ..These findings suggest that NAB2 mRNA 3'-end formation requires the exosome and TRAMP complex, and that competition between polyadenylation and Rrp6p-dependent degradation controls the level of this mRNA. ..
  27. Hackmann A, Wu H, Schneider U, Meyer K, Jung K, Krebber H. Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1. Nat Commun. 2014;5:3123 pubmed publisher
    ..Altogether, these data identify a role for shuttling SR proteins in mRNA surveillance and nuclear mRNA quality control. ..
  28. Tudek A, Porrúa O, Kabzinski T, Lidschreiber M, Kubicek K, Fortova A, et al. Molecular basis for coordinating transcription termination with noncoding RNA degradation. Mol Cell. 2014;55:467-81 pubmed publisher
    ..The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation...
  29. Barnard E, McFerran N, Trudgett A, Nelson J, Timson D. Detection and localisation of protein-protein interactions in Saccharomyces cerevisiae using a split-GFP method. Fungal Genet Biol. 2008;45:597-604 pubmed publisher
  30. Bernstein K, Granneman S, Lee A, Manickam S, Baserga S. Comprehensive mutational analysis of yeast DEXD/H box RNA helicases involved in large ribosomal subunit biogenesis. Mol Cell Biol. 2006;26:1195-208 pubmed
    ..a series of five mutations were created in each of the eight essential RNA helicases (Has1, Dbp6, Dbp10, Mak5, Mtr4, Drs1, Spb4, and Dbp9) involved in 60S ribosomal subunit biogenesis...
  31. Daoud R, Forget L, Lang B. Yeast mitochondrial RNase P, RNase Z and the RNA degradosome are part of a stable supercomplex. Nucleic Acids Res. 2012;40:1728-36 pubmed publisher
    ..Finally, the question of mt-RNase P localization within mitochondria was investigated, by GFP-tracing of a known protein subunit (Rpm2p). We find that about equal fractions of RNase P are soluble versus membrane-attached. ..
  32. Thoms M, Thomson E, Baßler J, Gnädig M, Griesel S, Hurt E. The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins. Cell. 2015;162:1029-38 pubmed publisher
    ..We report the identification of adaptor proteins that recruit the exosome-associated helicase, Mtr4, to unique RNA substrates...
  33. 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. ..
  34. Pertschy B, Zisser G, Schein H, Köffel R, Rauch G, Grillitsch K, et al. Diazaborine treatment of yeast cells inhibits maturation of the 60S ribosomal subunit. Mol Cell Biol. 2004;24:6476-87 pubmed
  35. 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
    ..Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 ..
  36. Schuch B, Feigenbutz M, Makino D, Falk S, Basquin C, Mitchell P, et al. The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase. EMBO J. 2014;33:2829-46 pubmed publisher
    ..physically and functionally interacts with the Rrp6 exoribonuclease and its associated cofactor Rrp47, the helicase Mtr4 and Mpp6...