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

Aitor Garzia, Seyed Mehdi Jafarnejad, Cindy Meyer, Clément Chapat, Tasos Gogakos, Pavel Morozov, Mehdi Amiri, Maayan Shapiro, Henrik Molina, Thomas Tuschl () and Nahum Sonenberg ()
Additional contact information
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

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/ncomms16056 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16056

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms16056

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().