PXD011772-2

PXD011772 is an original dataset announced via ProteomeXchange.

Title	The RNA-binding ubiquitin ligase MKRN1 acts as a sensor for ribosome-associated quality control of poly(A)-translation
Description	Human 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.
HostingRepository	PRIDE
AnnounceDate	2019-10-25
AnnouncementXML	Submission_2019-10-25_04:53:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-21 00:25:36	ID requested
1	2019-08-19 02:33:50	announced
⏵ 2	2019-10-25 04:53:43	announced	2019-10-25: Updated publication reference for PubMed record(s): 31640799.
3	2024-10-22 04:50:33	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biological

submitter keyword: MKRN1, ubiquitylation, RNA binding, ribosome-associated quality control, poly(A), iCLIP, ubiquitin remnant profiling

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011772
     1. Label: PRIDE project
     2. Name: The RNA-binding ubiquitin ligase MKRN1 acts as a sensor for ribosome-associated quality control of poly(A)-translation