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PXD011772 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe RNA-binding ubiquitin ligase MKRN1 acts as a sensor for ribosome-associated quality control of poly(A)-translation
DescriptionHuman cells have evolved multiple quality control mechanisms to ensure protein homeostasis by detecting aberrant mRNAs and protein products which are condemned for rapid decay. Translating ribosomes that run into poly(A) tails are terminally stalled, followed by ribosome recycling and rapid decay of the truncated nascent polypeptide via the ribosome-associated quality control (RQC). Here, we demonstrate that the conserved RNA-binding E3 ubiquitin ligase Makorin Ring Finger Protein 1 (MKRN1) acts as a novel sensor of poly(A) sequences to initiate ribosome stalling in RQC. Using individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP), we show that MKRN1 is positioned upstream of A-rich stretches and poly(A) tails in mRNAs via interaction with the cytoplasmic poly(A)-binding protein (PABP). Ubiquitin remnant profiling uncovers PABP and ribosomal protein RPS10 as well as multiple translational regulators as main targets of MRKN1-mediated ubiquitylation. The modified lysine in RPS10 is distinct from the main target sites of ZNF598, the second E3 ubiquitin ligase involved in initial ribosome stalling, indicating that multiple modifications need to converge to prevent promiscuous ubiquitylation of lysine-translating ribosomes. We propose that MKRN1 serves as a first line of poly(A) recognition at the RNA level to prevent erroneous protein products and maintain proteome integrity.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPetra Beli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-11-21 00:25:36ID requested
12019-08-19 02:33:50announced
22019-10-25 04:53:43announced2019-10-25: Updated publication reference for PubMed record(s): 31640799.
Publication List
Hildebrandt A, Br, ü, ggemann M, R, ü, ckl, é C, Boerner S, Heidelberger JB, Busch A, H, ä, nel H, Voigt A, M, ö, ckel MM, Ebersberger S, Scholz A, Dold A, Schmid T, Ebersberger I, Roignant JY, Zarnack K, K, ö, nig J, Beli P, The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation. Genome Biol, 20(1):216(2019) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: MKRN1, ubiquitylation, RNA binding, ribosome-associated quality control, poly(A), iCLIP, ubiquitin remnant profiling
Contact List
Petra Beli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
lab head
Petra Beli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
dataset submitter
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