Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

Wasmuth, Elizabeth V.; Zinder, John C.; Zattas, Dimitrios; Das, Mom; Lima, Christopher D.

doi:10.7554/eLife.29062

Title: Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

Journal Article · Tue Jul 25 00:00:00 EDT 2017 · eLife

DOI:https://doi.org/10.7554/eLife.29062· OSTI ID:1390869

Wasmuth, Elizabeth V. ^[1]; Zinder, John C. ^[2]; Zattas, Dimitrios ^[1]; Das, Mom ^[1];

^[3]

Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Tri-Institutional Training Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, United States
Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States

Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1390869

Journal Information:: eLife, Vol. 6, Issue 07, 2017; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.

Country of Publication:: United States

Language:: ENGLISH

References (60)

Structural analysis of the yeast exosome Rrp6p–Rrp47p complex by small-angle X-ray scattering Dedic, Emil; Seweryn, Paulina; Jonstrup, Anette Thyssen Biochemical and Biophysical Research Communications, Vol. 450, Issue 1 https://doi.org/10.1016/j.bbrc.2014.06.032	journal	July 2014
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 Stuparevic, Igor; Mosrin-Huaman, Christine; Hervouet-Coste, Nadège Journal of Biological Chemistry, Vol. 288, Issue 44 https://doi.org/10.1074/jbc.M113.491290	journal	September 2013
The 3' to 5' Exoribonuclease DIS3: From Structure and Mechanisms to Biological Functions and Role in Human Disease Robinson, Sophie; Oliver, Antony; Chevassut, Timothy Biomolecules, Vol. 5, Issue 3 https://doi.org/10.3390/biom5031515	journal	July 2015
Transcriptome-wide Analysis of Exosome Targets Schneider, Claudia; Kudla, Grzegorz; Wlotzka, Wiebke Molecular Cell, Vol. 48, Issue 3 https://doi.org/10.1016/j.molcel.2012.08.013	journal	November 2012
RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity Pefanis, Evangelos; Wang, Jiguang; Rothschild, Gerson Cell, Vol. 161, Issue 4 https://doi.org/10.1016/j.cell.2015.04.034	journal	May 2015
Structure of an Rrp6–RNA exosome complex bound to poly(A) RNA Wasmuth, Elizabeth V.; Januszyk, Kurt; Lima, Christopher D. Nature, Vol. 511, Issue 7510 https://doi.org/10.1038/nature13406	journal	July 2014
Exo- and Endoribonucleolytic Activities of Yeast Cytoplasmic and Nuclear RNA Exosomes Are Dependent on the Noncatalytic Core and Central Channel Wasmuth, Elizabeth V.; Lima, Christopher D. Molecular Cell, Vol. 48, Issue 1 https://doi.org/10.1016/j.molcel.2012.07.012	journal	October 2012
The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions Han, Jaeil; van Hoof, Ambro Cell Reports, Vol. 16, Issue 12 https://doi.org/10.1016/j.celrep.2016.08.059	journal	September 2016
Clustal W and Clustal X version 2.0 Larkin, M. A.; Blackshields, G.; Brown, N. P. Bioinformatics, Vol. 23, Issue 21, p. 2947-2948 https://doi.org/10.1093/bioinformatics/btm404	journal	September 2007
Assembly of the Yeast Exoribonuclease Rrp6 with Its Associated Cofactor Rrp47 Occurs in the Nucleus and Is Critical for the Controlled Expression of Rrp47 Feigenbutz, Monika; Jones, Rebecca; Besong, Tabot M. D. Journal of Biological Chemistry, Vol. 288, Issue 22 https://doi.org/10.1074/jbc.M112.445759	journal	April 2013
C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing Schilders, G.; van Dijk, E.; Pruijn, G. J. M. Nucleic Acids Research, Vol. 35, Issue 8 https://doi.org/10.1093/nar/gkm082	journal	March 2007
Degradation of ribosomal RNA precursors by the exosome Allmang, C. Nucleic Acids Research, Vol. 28, Issue 8 https://doi.org/10.1093/nar/28.8.1684	journal	April 2000
Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing Wang, H. -W.; Wang, J.; Ding, F. Proceedings of the National Academy of Sciences, Vol. 104, Issue 43 https://doi.org/10.1073/pnas.0705526104	journal	October 2007
Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors Zinder, John C.; Lima, Christopher D. Genes & Development, Vol. 31, Issue 2 https://doi.org/10.1101/gad.294769.116	journal	January 2017
Exosome Cofactors Connect Transcription Termination to RNA Processing by Guiding Terminated Transcripts to the Appropriate Exonuclease within the Nuclear Exosome Kim, Kyumin; Heo, Dong-hyuk; Kim, Iktae Journal of Biological Chemistry, Vol. 291, Issue 25 https://doi.org/10.1074/jbc.M116.715771	journal	April 2016
Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds Mumberg, Dominik; Müller, Rolf; Funk, Martin Gene, Vol. 156, Issue 1 https://doi.org/10.1016/0378-1119(95)00037-7	journal	April 1995
The Yeast Exosome Functions as a Macromolecular Cage to Channel RNA Substrates for Degradation Bonneau, Fabien; Basquin, Jérôme; Ebert, Judith Cell, Vol. 139, Issue 3 https://doi.org/10.1016/j.cell.2009.08.042	journal	October 2009
Reconstitution, Activities, and Structure of the Eukaryotic RNA Exosome Liu, Quansheng; Greimann, Jaclyn C.; Lima, Christopher D. Cell, Vol. 127, Issue 6 https://doi.org/10.1016/j.cell.2006.10.037	journal	December 2006
Nuclear Proximity of Mtr4 to RNA Exosome Restricts DNA Mutational Asymmetry Lim, Junghyun; Giri, Pankaj Kumar; Kazadi, David Cell, Vol. 169, Issue 3 https://doi.org/10.1016/j.cell.2017.03.043	journal	April 2017
The PMC2NT domain of the catalytic exosome subunit Rrp6p provides the interface for binding with its cofactor Rrp47p, a nucleic acid-binding protein Stead, Jonathan A.; Costello, Joe L.; Livingstone, Michaela J. Nucleic Acids Research, Vol. 35, Issue 16 https://doi.org/10.1093/nar/gkm614	journal	August 2007
RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex LaCava, John; Houseley, Jonathan; Saveanu, Cosmin Cell, Vol. 121, Issue 5 https://doi.org/10.1016/j.cell.2005.04.029	journal	June 2005
Functions of the exosome in rRNA, snoRNA and snRNA synthesis Allmang, C. The EMBO Journal, Vol. 18, Issue 19 https://doi.org/10.1093/emboj/18.19.5399	journal	October 1999
RNA degradation paths in a 12-subunit nuclear exosome complex Makino, Debora Lika; Schuch, Benjamin; Stegmann, Elisabeth Nature, Vol. 524, Issue 7563 https://doi.org/10.1038/nature14865	journal	July 2015
Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex Makino, Debora Lika; Baumgärtner, Marc; Conti, Elena Nature, Vol. 495, Issue 7439 https://doi.org/10.1038/nature11870	journal	February 2013
AU Binding Proteins Recruit the Exosome to Degrade ARE-Containing mRNAs Chen, Ching-Yi; Gherzi, Roberto; Ong, Shao-En Cell, Vol. 107, Issue 4 https://doi.org/10.1016/S0092-8674(01)00578-5	journal	November 2001
The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins Thoms, Matthias; Thomson, Emma; Baßler, Jochen Cell, Vol. 162, Issue 5 https://doi.org/10.1016/j.cell.2015.07.060	journal	August 2015
Visualization of distinct substrate-recruitment pathways in the yeast exosome by EM Liu, Jun-Jie; Bratkowski, Matthew A.; Liu, Xueqi Nature Structural & Molecular Biology, Vol. 21, Issue 1 https://doi.org/10.1038/nsmb.2736	journal	December 2013
The Exosome Cofactor Rrp47 Is Critical for the Stability and Normal Expression of Its Associated Exoribonuclease Rrp6 in Saccharomyces cerevisiae Feigenbutz, Monika; Garland, William; Turner, Martin PLoS ONE, Vol. 8, Issue 11 https://doi.org/10.1371/journal.pone.0080752	journal	November 2013
A strategy for dissecting the architectures of native macromolecular assemblies Shi, Yi; Pellarin, Riccardo; Fridy, Peter C. Nature Methods, Vol. 12, Issue 12 https://doi.org/10.1038/nmeth.3617	journal	October 2015
MPP6 is an exosome-associated RNA-binding protein involved in 5.8S rRNA maturation Schilders, G. Nucleic Acids Research, Vol. 33, Issue 21 https://doi.org/10.1093/nar/gki982	journal	November 2005
Cryptic Pol II Transcripts Are Degraded by a Nuclear Quality Control Pathway Involving a New Poly(A) Polymerase Wyers, Françoise; Rougemaille, Mathieu; Badis, Gwenaël Cell, Vol. 121, Issue 5 https://doi.org/10.1016/j.cell.2005.04.030	journal	June 2005
Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex Kowalinski, Eva; Kögel, Alexander; Ebert, Judith Molecular Cell, Vol. 63, Issue 1 https://doi.org/10.1016/j.molcel.2016.05.028	journal	July 2016
Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants Assenholt, J.; Mouaikel, J.; Andersen, K. R. RNA, Vol. 14, Issue 11 https://doi.org/10.1261/rna.1108008	journal	September 2008
Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex Lubas, Michal; Christensen, Marianne S.; Kristiansen, Maiken S. Molecular Cell, Vol. 43, Issue 4 https://doi.org/10.1016/j.molcel.2011.06.028	journal	August 2011
The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome Wasmuth, Elizabeth V.; Lima, Christopher D. Nucleic Acids Research, Vol. 45, Issue 2 https://doi.org/10.1093/nar/gkw1152	journal	November 2016
A New Yeast Poly(A) Polymerase Complex Involved in RNA Quality Control Vaňáčová, Štěpánka; Wolf, Jeannette; Martin, Georges PLoS Biology, Vol. 3, Issue 6 https://doi.org/10.1371/journal.pbio.0030189	journal	April 2005
The Jpred 3 secondary structure prediction server Cole, C.; Barber, J. D.; Barton, G. J. Nucleic Acids Research, Vol. 36, Issue Web Server https://doi.org/10.1093/nar/gkn238	journal	May 2008
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration Wan, Jijun; Yourshaw, Michael; Mamsa, Hafsa Nature Genetics, Vol. 44, Issue 6 https://doi.org/10.1038/ng.2254	journal	April 2012
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
RNA channelling by the eukaryotic exosome Malet, Hélène; Topf, Maya; Clare, Daniel K. EMBO reports, Vol. 11, Issue 12 https://doi.org/10.1038/embor.2010.164	journal	November 2010
The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates Basu, Uttiya; Meng, Fei-Long; Keim, Celia Cell, Vol. 144, Issue 3 https://doi.org/10.1016/j.cell.2011.01.001	journal	February 2011
Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3 Zinder, John C.; Wasmuth, Elizabeth V.; Lima, Christopher D. Molecular Cell, Vol. 64, Issue 4 https://doi.org/10.1016/j.molcel.2016.09.038	journal	November 2016
RNA-quality control by the exosome Houseley, Jonathan; LaCava, John; Tollervey, David Nature Reviews Molecular Cell Biology, Vol. 7, Issue 7 https://doi.org/10.1038/nrm1964	journal	July 2006
The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L Tomecki, Rafal; Kristiansen, Maiken S.; Lykke-Andersen, Søren The EMBO Journal, Vol. 29, Issue 14 https://doi.org/10.1038/emboj.2010.121	journal	June 2010
Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia Halevy, Ayelet; Lerer, Israela; Cohen, Rony Journal of Neurology, Vol. 261, Issue 11 https://doi.org/10.1007/s00415-014-7457-x	journal	August 2014
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy Lohr, Jens G.; Stojanov, Petar; Carter, Scott L. Cancer Cell, Vol. 25, Issue 1 https://doi.org/10.1016/j.ccr.2013.12.015	journal	January 2014
The exosome‐binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase Schuch, Benjamin; Feigenbutz, Monika; Makino, Debora L. The EMBO Journal, Vol. 33, Issue 23 https://doi.org/10.15252/embj.201488757	journal	October 2014
Version 1.2 of the Crystallography and NMR system Brunger, Axel T. Nature Protocols, Vol. 2, Issue 11 https://doi.org/10.1038/nprot.2007.406	journal	October 2007
A Yeast Exosome Cofactor, Mpp6, Functions in RNA Surveillance and in the Degradation of Noncoding RNA Transcripts Milligan, Laura; Decourty, Laurence; Saveanu, Cosmin Molecular and Cellular Biology, Vol. 28, Issue 17 https://doi.org/10.1128/MCB.00463-08	journal	June 2008
ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids Ashkenazy, H.; Erez, E.; Martz, E. Nucleic Acids Research, Vol. 38, Issue Web Server https://doi.org/10.1093/nar/gkq399	journal	May 2010
Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast Fasken, Milo B.; Losh, Jillian S.; Leung, Sara W. Genetics, Vol. 205, Issue 1 https://doi.org/10.1534/genetics.116.195917	journal	October 2016
Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae Watts, Sheldon G.; Crowder, Justin J.; Coffey, Samuel Z. Journal of Visualized Experiments, Issue 96 https://doi.org/10.3791/52428	journal	January 2015
Jalview Version 2--a multiple sequence alignment editor and analysis workbench Waterhouse, A. M.; Procter, J. B.; Martin, D. M. A. Bioinformatics, Vol. 25, Issue 9 https://doi.org/10.1093/bioinformatics/btp033	journal	January 2009
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Rrp6p Controls mRNA Poly(A) Tail Length and Its Decoration with Poly(A) Binding Proteins Schmid, Manfred; Poulsen, Mathias Bach; Olszewski, Pawel Molecular Cell, Vol. 47, Issue 2 https://doi.org/10.1016/j.molcel.2012.05.005	journal	July 2012
The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro Drążkowska, Karolina; Tomecki, Rafał; Stoduś, Krystian Nucleic Acids Research, Vol. 41, Issue 6 https://doi.org/10.1093/nar/gkt060	journal	February 2013
The regulation and functions of the nuclear RNA exosome complex Kilchert, Cornelia; Wittmann, Sina; Vasiljeva, Lidia Nature Reviews Molecular Cell Biology, Vol. 17, Issue 4 https://doi.org/10.1038/nrm.2015.15	journal	January 2016
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007

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