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

  1. Elizabeth V Wasmuth
  2. John C Zinder
  3. Dimitrios Zattas
  4. Mom Das
  5. Christopher D Lima  Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States

Abstract

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.

Data availability

The following data sets were generated
    1. Lima et al.
    (2017) Atomic coordinates and structure factors
    Publicly available at the RCSB Protein Data Bank (Accession no: 5VZJ).
The following previously published data sets were used

Article and author information

Author details

  1. Elizabeth V Wasmuth

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. John C Zinder

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dimitrios Zattas

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mom Das

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Christopher D Lima

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    LimaC@MSKCC.ORG
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9163-6092

Funding

Howard Hughes Medical Institute

  • Christopher D Lima

National Institutes of Health (R35GM118080)

  • Christopher D Lima

National Institutes of Health (R01GM079196)

  • Christopher D Lima

National Institutes of Health (F31GM097910)

  • Elizabeth V Wasmuth

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Wasmuth et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,230
    views
  • 526
    downloads
  • 52
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Elizabeth V Wasmuth
  2. John C Zinder
  3. Dimitrios Zattas
  4. Mom Das
  5. Christopher D Lima
(2017)
Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase
eLife 6:e29062.
https://doi.org/10.7554/eLife.29062

Share this article

https://doi.org/10.7554/eLife.29062