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The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

Author

Listed:
  • Aitor Garzia

    (Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University)

  • Seyed Mehdi Jafarnejad

    (McGill University)

  • Cindy Meyer

    (Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University)

  • Clément Chapat

    (McGill University)

  • Tasos Gogakos

    (Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University)

  • Pavel Morozov

    (Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University)

  • Mehdi Amiri

    (McGill University)

  • Maayan Shapiro

    (McGill University)

  • Henrik Molina

    (Proteomics Resource Center, The Rockefeller University)

  • Thomas Tuschl

    (Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University)

  • Nahum Sonenberg

    (McGill University)

Abstract

Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNALys(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC.

Suggested Citation

  • Aitor Garzia & Seyed Mehdi Jafarnejad & Cindy Meyer & Clément Chapat & Tasos Gogakos & Pavel Morozov & Mehdi Amiri & Maayan Shapiro & Henrik Molina & Thomas Tuschl & Nahum Sonenberg, 2017. "The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16056
    DOI: 10.1038/ncomms16056
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    Cited by:

    1. Momoko Narita & Timo Denk & Yoshitaka Matsuo & Takato Sugiyama & Chisato Kikuguchi & Sota Ito & Nichika Sato & Toru Suzuki & Satoshi Hashimoto & Iva Machová & Petr Tesina & Roland Beckmann & Toshifumi, 2022. "A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Ken Ikeuchi & Nives Ivic & Robert Buschauer & Jingdong Cheng & Thomas Fröhlich & Yoshitaka Matsuo & Otto Berninghausen & Toshifumi Inada & Thomas Becker & Roland Beckmann, 2023. "Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Malgorzata J. Latallo & Shaopeng Wang & Daoyuan Dong & Blake Nelson & Nathan M. Livingston & Rong Wu & Ning Zhao & Timothy J. Stasevich & Michael C. Bassik & Shuying Sun & Bin Wu, 2023. "Single-molecule imaging reveals distinct elongation and frameshifting dynamics between frames of expanded RNA repeats in C9ORF72-ALS/FTD," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Ji Geng & Shuangxi Li & Yu Li & Zhihao Wu & Sunil Bhurtel & Suman Rimal & Danish Khan & Rani Ohja & Onn Brandman & Bingwei Lu, 2024. "Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Katharina Best & Ken Ikeuchi & Lukas Kater & Daniel Best & Joanna Musial & Yoshitaka Matsuo & Otto Berninghausen & Thomas Becker & Toshifumi Inada & Roland Beckmann, 2023. "Structural basis for clearing of ribosome collisions by the RQT complex," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Jiangnan Liu & Noemi Nagy & Carlos Ayala-Torres & Francisco Aguilar-Alonso & Francisco Morais-Esteves & Shanshan Xu & Maria G. Masucci, 2023. "Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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