CoChat
Sign Up
Cited by 5RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

In vivo characterization of the critical interaction between the RNA exosome and the essential RNA helicase Mtr4 in Saccharomyces cerevisiae

Open access
Sterrett, Maria C, Farchi, Daniela, Strassler, Sarah E, Boise, Lawrence H, Fasken, Milo B, Corbett, Anita H·2023·G3: Genes, Genomes, Genetics
DOI 10.1093/g3journal/jkad049PMC PMC10411580
Open this paper in CoChat — free accountOpen PDF

Abstract

The RNA exosome is a conserved molecular machine that processes/degrades numerous coding and non-coding RNAs. The 10-subunit complex is composed of three S1/KH cap subunits (human EXOSC2/3/1; yeast Rrp4/40/Csl4), a lower ring of six PH-like subunits (human EXOSC4/7/8/9/5/6; yeast Rrp41/42/43/45/46/Mtr3), and a singular 3′-5′ exo/endonuclease DIS3/Rrp44. Recently, several disease-linked missense mutations have been identified in structural cap and core RNA exosome genes. In this study, we characterize a rare multiple myeloma patient missense mutation that was identified in the cap subunit gene EXOSC2. This missense mutation results in a single amino acid substitution, p.Met40Thr, in a highly conserved domain of EXOSC2. Structural studies suggest that this Met40 residue makes direct contact with the essential RNA helicase, MTR4, and may help stabilize the critical interaction between the RNA exosome complex and this cofactor. To assess this interaction in vivo, we utilized the Saccharomyces cerevisiae system and modeled the EXOSC2 patient mutation into the orthologous yeast gene RRP4, generating the variant rrp4-M68T. The rrp4-M68T cells show accumulation of certain RNA exosome target RNAs and show sensitivity to drugs that impact RNA processing. We also identified robust negative genetic interactions between rrp4-M68T and specific mtr4 mutants. A complementary biochemical approach revealed that Rrp4 M68T shows decreased interaction with Mtr4, consistent with these genetic results. This study suggests that the EXOSC2 mutation identified in a multiple myeloma patient impacts the function of the RNA exosome and provides functional insight into a critical interface between the RNA exosome and Mtr4.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/g3journal/jkad049

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Many transcripts differentially expressed in all five datasets were noncoding RNAs, which are well established targets for the RNA exosome and can include PROMPTs, antisense transcripts, and long noncoding RNAs.

    “Many of the transcripts that were differentially expressed in all five datasets were noncoding RNAs, which are well established to be targets for the RNA exosome and can include PROMPTs, antisense (AS) transcripts, and long noncoding RNAs (lncRNAs) as shown in Fig. 2B61–67.”

    From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [61]

    The Introduction (page unavailable) says the RNA exosome processes small noncoding RNAs and targets transcripts from pervasive transcription for degradation, explicitly including human PROMPTs. It does not identify antisense transcripts or lncRNAs as examples, and it does not report the citing authors’ five-dataset comparison. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 91

  1. Adams A, Gottschling DE, Kaiser CA, Stearns T. Methods in Yeast Genetics. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997.
  2. Alexander DD, Mink PJ, Adami HO, Cole P, Mandel JS, Oken MM, Trichopoulos D. Multiple myeloma: a review of the epidemiologic literature. Int J Cancer. 2007; 120(S12): 40– 61. doi: 10.1002/ijc.22718. 17405120 · DOI
  3. Allmang C, Kufel J, Chanfreau G, Mitchell P, Petfalski E, et al Functions of the exosome in rRNA, snoRNA and snRNA synthesis. Embo J. 1999; 18(19): 5399– 5410. doi: 10.1093/emboj/18.19.5399. 10508172 PMC1171609 · DOI
  4. Anderson JT, Wang X. Nuclear RNA surveillance: no sign of substrates tailing off. Crit Rev Biochem Mol Biol. 2009; 44(1): 16– 24. doi: 10.1080/10409230802640218. 19280429 · DOI
  5. Ashkenazy H, Abadi S, Martz E, Chay O, Mayrose I, Pupko T, Ben-Tal N. Consurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res. 2016; 44(W1): W344– W350. doi: 10.1093/nar/gkw408. 27166375 PMC4987940 · DOI · Paper page
  6. Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal N. Consurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 2010; 38(Web Server): W529– W533. doi: 10.1093/nar/gkq399. 20478830 PMC2896094 · DOI
  7. Barwick BG, Neri P, Bahlis NJ, Nooka AK, Dhodapkar MV, Jaye DL, Hofmeister CC, Kaufman JL, Gupta VA, Auclair D, et al Multiple myeloma immunoglobulin lambda translocations portend poor prognosis. Nat Commun. 2019; 10(1): 1911. doi: 10.1038/s41467-019-09555-6. 31015454 PMC6478743 · DOI
  8. Belair C, Sim S, Kim KY, Tanaka Y, Park IH, Wolin SL. The RNA exosome nuclease complex regulates human embryonic stem cell differentiation. J Cell Biol. 2019; 218(8): 2564– 2582. doi: 10.1083/jcb.201811148. 31308215 PMC6683745 · DOI
  9. Belair C, Sim S, Wolin SL. Noncoding RNA surveillance: the ends justify the means. Chem Rev. 2018; 118(8): 4422– 4447. doi: 10.1021/acs.chemrev.7b00462. 29023106 PMC8071604 · DOI
  10. Bergsagel PL, Nardini E, Brents L, Chesi M, Kuehl WM. Igh translocations in multiple myeloma: a nearly universal event that rarely involves c-myc. Curr Top Microbiol Immunol. 1997; 224: 283– 287. doi: 10.1007/978-3-642-60801-8_30. 9308253 · DOI
  11. Boczonadi V, Mueller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, et al EXOSC8 Mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014; 5(1): 4287. doi: 10.1038/ncomms5287. 24989451 PMC4102769 · DOI · Paper page
  12. Boyle EM, Ashby C, Tytarenko RG, Deshpande S, Wang H, Wang Y, Rosenthal A, Sawyer J, Tian E, Flynt E, et al BRAF and DIS3 mutations associate with adverse outcome in a long-term follow-up of patients with multiple myeloma. Clin Cancer Res. 2020; 26(10): 2422– 2432. doi: 10.1158/1078-0432.CCR-19-1507. 31988198 · DOI
  13. Briggs MW, Burkard KT, Butler JS. Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3′ end formation. J Biol Chem. 1998; 273(21): 13255– 13263. doi: 10.1074/jbc.273.21.13255. 9582370 · DOI
  14. Burns D, Donkervoort D, Bharucha-Goebel D, Giunta M, Munro B, Scavina M, Foley R, Müller JS, Bönnemann CG, Horvath R. A recessive mutation in EXOSC9 causes abnormal RNA metabolism resulting in a novel form of cerebellar hypoplasia/atrophy with early motor neuronopathy. Neuromuscul Disord. 2017; 27: S38. doi: 10.1016/S0960-8966(17)30331-0. · DOI
  15. Burns DT, Donkervoort S, Muller JS, Knierim E, Bharucha-Goebel D, Faqeih EA, Bell SK, AlFaifi AY, Monies D, Millan F, et al Variants in EXOSC9 disrupt the RNA exosome and result in cerebellar atrophy with spinal motor neuronopathy. Am J Hum Genet. 2018; 102(5): 858– 873. doi: 10.1016/j.ajhg.2018.03.011. 29727687 PMC5986733 · DOI · Paper page
  16. Büttner K, Nehring S, Hopfner KP. Structural basis for DNA duplex separation by a superfamily-2 helicase. Nat Struct Mol Biol. 2007; 14(7): 647– 652. doi: 10.1038/nsmb1246. 17558417 · DOI
  17. Celniker G, Nimrod G, Ashkenazy H, Glaser F, Martz E, Mayrose I, Pupko T, Ben-Tal N. Consurf: using evolutionary data to raise testable hypotheses about protein function. Israel J Chem. 2013; 53(3–4): 199– 206. doi: 10.1002/ijch.201200096. · DOI
  18. Cervelli T, Galli A. Yeast as a tool to understand the significance of human disease-associated gene variants. Genes (Basel). 2021; 12(9): 1303. doi: 10.3390/genes12091303. 34573285 PMC8465565 · DOI
  19. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet J-P, Ahmann GJ, Adli M, et al Initial genome sequencing and analysis of multiple myeloma. Nature. 2011; 471(7339): 467– 472. doi: 10.1038/nature09837. 21430775 PMC3560292 · DOI
  20. Cherry JM, Hong EL, Amundsen C, Balakrishnan R, Binkley G, Chan ET, Christie KR, Costanzo MC, Dwight SS, Engel SR, et al Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res. 2012; 40(D1): D700– D705. doi: 10.1093/nar/gkr1029. 22110037 PMC3245034 · DOI
  21. Coy S, Volanakis A, Shah S, Vasiljeva L. The Sm complex is required for the processing of non-coding RNAs by the exosome. PloS one. 2013; 8(6): e65606– e65606. doi: 10.1371/journal.pone.0065606. 23755256 PMC3675052 · DOI
  22. de Amorim J, Slavotinek A, Fasken MB, Corbett AH, Morton DJ. Modeling pathogenic variants in the RNA exosome. RNA & Dis. 2020; 7: e1166. PMCID: PMC8528344 PMC8528344 34676290
  23. 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(4): 1128– 1140. doi: 10.1093/emboj/17.4.1128. 9463390 PMC1170461 · DOI
  24. Delan-Forino C, Schneider C, Tollervey D. Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex. PLOS Genet. 2017; 13(3): e1006699. doi: 10.1371/journal.pgen.1006699. 28355211 PMC5389853 · DOI
  25. Di Donato N, Neuhann T, Kahlert A-K, Klink B, Hackmann K, Neuhann I, Novotna B, Schallner J, Krause C, Glass IA, et al Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt. J Med Genet. 2016; 53(6): 419– 425. doi: 10.1136/jmedgenet-2015-103511. 26843489 · DOI
  26. Donahue TF, Henry SA. myo-Inositol-1-phosphate synthase. Characteristics of the enzyme and identification of its structural gene in yeast. J Biol Chem. 1981; 256(13): 7077– 7085. doi: 10.1016/S0021-9258(19)69102-7. 7016881 · DOI
  27. Eggens VRC, Barth PG, Niermeijer J-MF, Berg JN, Darin N, Dixit A, Fluss J, Foulds N, Fowler D, Hortobágyi T, et al EXOSC3 Mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. Orphanet J Rare Dis. 2014; 9(1): 23. doi: 10.1186/1750-1172-9-23. 24524299 PMC3928094 · DOI
  28. Falk S, Weir JR, 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(6): 856– 867. doi: 10.1016/j.molcel.2014.07.020. 25175027 · DOI
  29. Fasken MB, Losh JS, Leung SW, Brutus S, Avin B, Vaught JC, Potter-Birriel J, Craig T, Conn GL, Mills-Lujan K, et al Insight into the RNA exosome complex through modeling pontocerebellar hypoplasia type 1b disease mutations in yeast. Genetics. 2017; 205(1): 221– 237. doi: 10.1534/genetics.116.195917. 27777260 PMC5223504 · DOI · Paper page
  30. Fasken MB, Morton DJ, Kuiper EG, Jones SK, Leung SW, Corbett AH. The RNA exosome and human disease. Methods Mol Biol. 2020; 2062: 3– 33. doi: 10.1007/978-1-4939-9822-7_1. 31768969 · DOI
  31. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS. Global analysis of protein expression in yeast. Nature. 2003; 425(6959): 737– 741. doi: 10.1038/nature02046. 14562106 · DOI · Paper page
  32. Giaever G, Flaherty P, Kumm J, Proctor M, Nislow C, Jaramillo DF, Chu AM, Jordan MI, Arkin AP, Davis RW. Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. Proc Natl Acad Sci U S A. 2004; 101(3): 793– 798. doi: 10.1073/pnas.0307490100. 14718668 PMC321760 · DOI
  33. Gillespie A, Gabunilas J, Jen JC, Chanfreau GF. Mutations of EXOSC3/Rrp40p associated with neurological diseases impact ribosomal RNA processing functions of the exosome in S. cerevisiae. RNA. 2017; 23(4): 466– 472. doi: 10.1261/rna.060004.116. 28053271 PMC5340910 · DOI · Paper page
  34. Hoskins J, Scott Butler J. Evidence for distinct DNA- and RNA-based mechanisms of 5-fluorouracil cytotoxicity in Saccharomyces cerevisiae. Yeast. 2007; 24(10): 861– 870. doi: 10.1002/yea.1516. 17640085 · DOI
  35. Hou D, Ruiz M, Andrulis ED. The ribonuclease Dis3 is an essential regulator of the developmental transcriptome. Bmc Genomics. 2012; 13(1): 359. doi: 10.1186/1471-2164-13-359. 22853036 PMC3434026 · DOI
  36. Houseley J, LaCava J, Tollervey D. RNA-quality control by the exosome. Nat Rev Mol Cell Biol. 2006; 7(7): 529– 539. doi: 10.1038/nrm1964. 16829983 · DOI
  37. Houseley J, Tollervey D. The nuclear RNA surveillance machinery: the link between ncRNAs and genome structure in budding yeast? Biochim Biophys Acta. 2008; 1779(4): 239– 246. doi: 10.1016/j.bbagrm.2007.12.008. 18211833 · DOI
  38. Houseley J, Tollervey D. The many pathways of RNA degradation. Cell. 2009; 136(4): 763– 776. doi: 10.1016/j.cell.2009.01.019. 19239894 · DOI
  39. Hoyos-Manchado R, Reyes-Martín F, Rallis C, Gamero-Estévez E, Rodríguez-Gómez P, Quintero-Blanco J, Bähler J, Jiménez J, Tallada VA. RNA metabolism is the primary target of formamide in vivo. Sci Rep. 2017; 7(1): 15895. doi: 10.1038/s41598-017-16291-8. 29162938 PMC5698326 · DOI
  40. Jackson RN, Klauer AA, Hintze BJ, Robinson H, van Hoof A, Johnson SJ. The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing. EMBO J. 2010; 29(13): 2205– 2216. doi: 10.1038/emboj.2010.107. 20512111 PMC2905245 · DOI
  41. Kadowaki T, Chen S, Hitomi M, Jacobs E, Kumagai C, et al Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants. J Cell Biol. 1994; 126(3): 649– 659. doi: 10.1083/jcb.126.3.649. 8045930 PMC2120137 · DOI
  42. Kadowaki T, Schneiter R, Hitomi M, Tartakoff AM. Mutations in nucleolar proteins lead to nucleolar accumulation of polyA+ RNA in Saccharomyces cerevisiae. Mol Biol Cell. 1995; 6(9): 1103– 1110. doi: 10.1091/mbc.6.9.1103. 8534909 PMC301270 · DOI
  43. Kilchert C, Wittmann S, Vasiljeva L. The regulation and functions of the nuclear RNA exosome complex. Nat Rev Mol Cell Biol. 2016; 17(4): 227– 239. doi: 10.1038/nrm.2015.15. 26726035 · DOI
  44. Klig LS, Henry SA. Isolation of the yeast INO1 gene: located on an autonomously replicating plasmid, the gene is fully regulated. Proc Natl Acad Sci U S A. 1984; 81(12): 3816– 3820. doi: 10.1073/pnas.81.12.3816. 6374665 PMC345311 · DOI
  45. LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, Tollervey D. RNA degradation by the exosome is promoted by a nuclear polyade nylation complex. Cell. 2005; 121(5): 713– 724. doi: 10.1016/j.cell.2005.04.029. 15935758 · DOI
  46. Laubach J, Richardson P, Anderson K. Multiple myeloma. Annu Rev Med. 2011; 62(1): 249– 264. doi: 10.1146/annurev-med-070209-175325. 21090965 · DOI
  47. Liang S, Hitomi M, Hu YH, Liu Y, Tartakoff AM. A DEAD-box-family protein is required for nucleocytoplasmic transport of yeast mRNA. Mol Cell Biol. 1996; 16(9): 5139– 5146. doi: 10.1128/MCB.16.9.5139. 8756671 PMC231514 · DOI
  48. Lim SJ, Boyle PJ, Chinen M, Dale RK, Lei EP. Genome-wide localization of exosome components to active promoters and chromatin insulators in Drosophila. Nucleic Acids Res. 2013; 41(5): 2963– 2980. doi: 10.1093/nar/gkt037. 23358822 PMC3597698 · DOI
  49. Lim J, Giri PK, Kazadi D, Laffleur B, Zhang W, Grinstein V, Pefanis E, Brown LM, Ladewig E, Martin O, et al Nuclear proximity of Mtr4 to RNA exosome restricts DNA mutational asymmetry. Cell. 2017; 169(3): 523– 537 e515. doi: 10.1016/j.cell.2017.03.043. 28431250 PMC5515252 · DOI
  50. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001; 25(4): 402– 408. doi: 10.1006/meth.2001.1262. 11846609 · DOI · Paper page
  51. Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, Sougnez C, Knoechel B, Gould J, Saksena G, et al Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014; 25(1): 91– 101. doi: 10.1016/j.ccr.2013.12.015. 24434212 PMC4241387 · DOI · Paper page
  52. Lorentzen E, Dziembowski A, Lindner D, Seraphin B, Conti E. RNA channelling by the archaeal exosome. EMBO Rep. 2007; 8(5): 470– 476. doi: 10.1038/sj.embor.7400945. 17380186 PMC1866195 · DOI
  53. Lubas M, Christensen MS, Kristiansen MS, Domanski M, Falkenby LG, Lykke-Andersen S, Andersen JS, Dziembowski A, Jensen TH. Interaction profiling identifies the human nuclear exosome targeting complex. Mol Cell. 2011; 43(4): 624– 637. doi: 10.1016/j.molcel.2011.06.028. 21855801 · DOI
  54. Makino DL, Baumgaertner M, Conti E. Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex. Nature. 2013; 495(7439): 70– 75. doi: 10.1038/nature11870. 23376952 · DOI
  55. Milligan L, Decourty L, Saveanu C, Rappsilber J, Ceulemans H, Jacquier A, Tollervey D. A yeast exosome cofactor, Mpp6, functions in RNA surveillance and in the degradation of noncoding RNA transcripts. Mol Cell Biol. 2008; 28(17): 5446– 5457. doi: 10.1128/MCB.00463-08. 18591258 PMC2519741 · DOI
  56. 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(19): 6982– 6992. doi: 10.1128/MCB.23.19.6982-6992.2003. 12972615 PMC193929 · DOI
  57. 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(4): 457– 466. doi: 10.1016/S0092-8674(00)80432-8. 9390555 · DOI
  58. Mitchell P, Petfalski E, Tollervey D. The 3′ end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism. Genes Dev. 1996; 10(4): 502– 513. doi: 10.1101/gad.10.4.502. 8600032 · DOI
  59. Moore MJ, Proudfoot NJ. Pre-mRNA processing reaches back to transcription and ahead to translation. Cell. 2009; 136(4): 688– 700. doi: 10.1016/j.cell.2009.02.001. 19239889 · DOI
  60. Oddone A, Lorentzen E, Basquin J, Gasch A, Rybin V, Conti E, Sattler M. Structural and biochemical characterization of the yeast exosome component Rrp40. EMBO Rep. 2007; 8(1): 63– 69. doi: 10.1038/sj.embor.7400856. 17159918 PMC1796750 · DOI · Paper page
  61. Ogami K, Chen Y, Manley JL. RNA Surveillance by the nuclear RNA exosome: mechanisms and significance. Noncoding RNA. 2018; 4(1): 8. doi: 10.3390/ncrna4010008. 29629374 PMC5886371 · DOI
  62. Parker R. RNA degradation in Saccharomyces cerevisae. Genetics. 2012; 191(3): 671– 702. doi: 10.1534/genetics.111.137265. 22785621 PMC3389967 · DOI
  63. Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, Schierup MH, Jensen TH. RNA exosome depletion reveals transcription upstream of active human promoters. Science. 2008; 322(5909): 1851– 1854. doi: 10.1126/science.1164096. 19056938 · DOI
  64. Rodríguez-Galán O, García-Gómez JJ, Kressler D, de la Cruz J. Immature large ribosomal subunits containing the 7S pre-rRNA can engage in translation in Saccharomyces cerevisiae. RNA Biol. 2015; 12(8): 838– 846. doi: 10.1080/15476286.2015.1058477. 26151772 PMC4615593 · DOI
  65. Rodrigues CHM, Myung Y, Pires DEV, Ascher DB. mCSM-PPI2: predicting the effects of mutations on protein-protein interactions. Nucleic Acids Res. 2019; 47(W1): W338– w344. doi: 10.1093/nar/gkz383. 31114883 PMC6602427 · DOI · Paper page
  66. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, Cold Spring Harbor; 1989.
  67. Schaeffer D, Tsanova B, Barbas A, Reis FP, Dastidar EG, Sanchez-Rotunno M, Arraiano CM, van Hoof A. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol. 2009; 16(1): 56– 62. doi: 10.1038/nsmb.1528. 19060898 PMC2615074 · DOI
  68. Schneider C, Kudla G, Wlotzka W, Tuck A, Tollervey D. Transcriptome-wide analysis of exosome targets. Mol Cell. 2012; 48(3): 422– 433. doi: 10.1016/j.molcel.2012.08.013. 23000172 PMC3526797 · DOI · Paper page
  69. Schneider C, Tollervey D. Threading the barrel of the RNA exosome. Trends Biochem Sci. 2013; 38(10): 485– 493. doi: 10.1016/j.tibs.2013.06.013. 23910895 PMC3838930 · DOI
  70. Schuch B, Feigenbutz M, Makino DL, Falk S, Basquin C, Mitchell P, Conti E. The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase. Embo J. 2014; 33(23): 2829– 2846. doi: 10.15252/embj.201488757. 25319414 PMC4282559 · DOI
  71. Schuller JM, Falk S, Fromm L, Hurt E, Conti E. Structure of the nuclear exosome captured on a maturing preribosome. Science. 2018; 360(6385): 219– 222. doi: 10.1126/science.aar5428. 29519915 · DOI
  72. Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1): 19– 27. doi: 10.1093/genetics/122.1.19. 2659436 PMC1203683 · DOI
  73. Slater ML. Effect of reversible inhibition of deoxyribonucleic acid synthesis on the yeast cell cycle. J Bacteriol. 1973; 113(1): 263– 270. doi: 10.1128/jb.113.1.263-270.1973. 4120066 PMC251626 · DOI
  74. Slavotinek A, Misceo D, Htun S, Mathisen L, Frengen E, Hurtig JE, Enyenihi L, Sterrett MC, Leung SW, Schneidman-Duhovny D, et al Biallelic variants in the RNA exosome gene EXOSC5 are associated with developmental delays, short stature, cerebellar hypoplasia and motor weakness. Hum Mol Genet. 2020; 29(13): 2218– 2239. doi: 10.1093/hmg/ddaa108. 32504085 PMC7399534 · DOI
  75. Somashekar PH, Kaur P, Stephen J, Guleria VS, Kadavigere R, Girisha KM, Bielas S, Upadhyai P, Shukla A. Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia. Clin Genet. 2021; 99(4): 594– 600. doi: 10.1111/cge.13928. 33463720 PMC9990822 · DOI · Paper page
  76. Staals RH, Bronkhorst AW, Schilders G, Slomovic S, Schuster G, Heck AJR, Raijmakers R, Pruijn GJM. Dis3-like 1: a novel exoribonuclease associated with the human exosome. Embo j. 2010; 29(14): 2358– 2367. doi: 10.1038/emboj.2010.122. 20531389 PMC2910272 · DOI
  77. Sterrett MC, Enyenihi L, Leung SW, Hess L, Strassler SE, Farchi D, Lee RS, Withers ES, Kremsky I, Baker RE, et al A budding yeast model for human disease mutations in the EXOSC2 cap subunit of the RNA exosome complex. RNA. 2021; 27(9): 1046– 1067. doi: 10.1261/rna.078618.120. 34162742 PMC8370739 · DOI
  78. Stuparevic I, Mosrin-Huaman C, Hervouet-Coste N, Remenaric M, Rahmouni AR. Cotranscriptional recruitment of RNA exosome cofactors Rrp47p and Mpp6p and two distinct Trf-Air-Mtr4 polyadenylation (TRAMP) complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant messenger ribonucleoprotein particle (mRNP) in yeast. J Biol Chem. 2013; 288(44): 31816– 31829. doi: 10.1074/jbc.M113.491290. 24047896 PMC3814775 · DOI
  79. Suzuki H, Nagai K, Akutsu E, Yamaki H, Tanaka N. On the mechanism of action of bleomycin. Strand scission of DNA caused by bleomycin and its binding to DNA in vitro. J Antibiot (Tokyo). 1970; 23(10): 473– 480. doi: 10.7164/antibiotics.23.473. 4991640 · DOI
  80. Taylor LL, Jackson RN, Rexhepaj M, King AK, Lott LK, van Hoof A, Johnson SJ. The Mtr4 ratchet helix and arch domain both function to promote RNA unwinding. Nucleic Acids Res. 2014; 42(22): 13861– 13872. doi: 10.1093/nar/gku1208. 25414331 PMC4267639 · DOI
  81. Tomecki R, Drazkowska K, Kucinski I, Stodus K, Szczesny RJ, Gruchota J, Owczarek EP, Kalisiak K, Dziembowski A. 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(2): 1270– 1290. doi: 10.1093/nar/gkt930. 24150935 PMC3902924 · DOI
  82. Vaňáčová Š, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, Langen H, Keith G, Keller W, et al A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 2005; 3(6): e189. doi: 0.1371/journal.pbio.0030189 15828860 PMC1079787
  83. 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(2): 441– 452. doi: 10.1128/MCB.20.2.441-452.2000. 10611222 PMC85098 · DOI
  84. Wan J, Yourshaw M, Mamsa H, Rudnik-Schöneborn S, Menezes MP, Hong JE, Leong DW, Senderek J, Salman MS, Chitayat D, et al Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet. 2012; 44(6): 704– 708. doi: 10.1038/ng.2254. 22544365 PMC3366034 · DOI · Paper page
  85. Wasmuth EV, Januszyk K, Lima CD. Structure of an Rrp6-RNA exosome complex bound to poly(A) RNA. Nature. 2014; 511(7510): 435– 439. doi: 10.1038/nature13406. 25043052 PMC4310248 · DOI
  86. Wasmuth EV, Zinder JC, Zattas D, Das M, Lima CD. Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase. Elife. 2017; 6: e29062. doi: 10.7554/eLife.29062. 28742025 PMC5553935 · DOI
  87. Weir JR, 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(27): 12139– 12144. doi: 10.1073/pnas.1004953107. 20566885 PMC2901443 · DOI
  88. Weissbach S, Langer C, Puppe B, Nedeva T, Bach E, Kull M, Bargou R, Einsele H, Rosenwald A, Knop S, et al The molecular spectrum and clinical impact of DIS3 mutations in multiple myeloma. Br J Haematol. 2015; 169(1): 57– 70. doi: 10.1111/bjh.13256. 25521164 · DOI
  89. Wyers F, Rougemaille M, Badis G, Rousselle J-C, Dufour M-E, Boulay J, Régnault B, Devaux F, Namane A, Séraphin B, et al Cryptic Pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell. 2005; 121(5): 725– 737. doi: 10.1016/j.cell.2005.04.030. 15935759 · DOI
  90. Yang X, Bayat V, DiDonato N, Zhao Y, Zarnegar B, Siprashvili Z, Lopez-Pajares V, Sun T, Tao S, Li C, et al Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis. Hum Mol Genet. 2019; 29(4): 541– 553. doi: 10.1093/hmg/ddz251. PMC7068030 31628467 · DOI
  91. Zinder JC, Lima CD. Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors. Genes Dev. 2017; 31(2): 88– 100. doi: 10.1101/gad.294769.116. 28202538 PMC5322736 · DOI

Cited by

Sorted by citations

Authors
Sterrett, M. C., Farchi, D., Strassler, S. E., Boise, L. H., Fasken, M. B., & Corbett, A. H.
Affiliations
Emory University (US)
Corresponding author
Corbett, Anita H
ORCID
Venue
G3: Genes, Genomes, Genetics
Publisher
Oxford University Press (OUP)
Published
2023-03-02
Volume
13
Issue
8
ISSN
2160-1836 (ISSN-L)
DOI
10.1093/g3journal/jkad049
PMC
PMC10411580
OpenAlex
W4322757088
Cited by
5
References
4
Citations by year
2026: 2 · 2024: 1 · 2023: 2
FWCI
0.45
Type
journal article
Language
en
Open access
Licence
Locations
  • G3 Genes Genomes Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (GM058728, CA273773)
  • National Institute of General Medical Sciences (GM134649-01)
  • National Science Foundation
  • Genetics Society of America
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RNA exosome, Mtr4, missense mutations, multiple myeloma, RNA helicase, protein-protein interaction, Saccharomyces cerevisiae, negative genetic interactions, RNA processing, RNA degradation, DIS3
MeSH terms
Exoribonucleases, Humans, Multiple Myeloma, RNA, Saccharomyces cerevisiae, RNA Helicases, Saccharomyces cerevisiae Proteins, DEAD-box RNA Helicases, Exosome Multienzyme Ribonuclease Complex

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review