PXD018316 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs |
Description | Nascent peptide chain targeting to the endoplasmic reticulum (ER) membrane is required for correct localization and efficient translation of membrane-bound and secreted proteins. However, little is known about the contribution of RNA-binding proteins (RBPs) to the recognition, localization and translation of ER-localized mRNAs. In this work we used biochemical, transcriptomic and proteomic approaches to delineate the role of human HDLBP. PAR-CLIP analysis revealed that HDLBP directly and specifically interacted with more than 80% of all expressed ER-localized mRNAs. Interestingly, the binding to the coding sequence was most prominent for ER-localized mRNAs, while cytosolic mRNAs showed higher binding in the 3’UTR. HDLBP crosslinked strongly to long CU-rich motifs that resided more frequently in coding sequences of ER-localized but not in cytosolic mRNAs. This indicated that the primary sequence composition determines the basis for HDLBP binding specificity and its multivalent interactions with ER-bound mRNAs. PAR-CLIP analysis also revealed direct interactions of HDLBP with the RNA components of the translational apparatus, while in vivo proximity proteomics detected proteins involved in translation and components of the signal recognition particle (SRP). Functional studies using CRISPR-Cas9 HDLBP knockout cell lines in combination with ribosome profiling, pSILAC, and luciferase assays showed decreased translation efficiency of HDLBP target mRNAs, impaired protein synthesis and secretion in the knockout conditions. Finally, HDLBP absence resulted in decrease of lung tumor formation capacity in vivo. These results highlight a general function for HDLBP in the translation of ER -localized mRNAs via the secretory pathway and discover its relevance for cell profileration and tumor progression |
HostingRepository | PRIDE |
AnnounceDate | 2022-05-09 |
AnnouncementXML | Submission_2022-05-09_06:29:29.818.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Carlos Vieira |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-01 05:04:09 | ID requested | |
⏵ 1 | 2022-05-09 06:29:30 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: HDLBP |
Vigilin |
RNA-binding protein |
KH-domain |
endoplasmic reticulum |
translation |
Contact List
Matthias Selbach |
contact affiliation | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Proteome Dynamics, Berlin, Germany |
contact email | matthias.selbach@mdc-berlin.de |
lab head | |
Carlos Vieira |
contact affiliation | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft |
contact email | carlos.vieira@mdc-berlin.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018316
- Label: PRIDE project
- Name: Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs