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PXD018313

PXD018313 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleVigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs
DescriptionNascent 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.
HostingRepositoryPRIDE
AnnounceDate2022-06-09
AnnouncementXMLSubmission_2022-06-09_02:44:04.232.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGuido Mastrobuoni
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-01 02:46:20ID requested
12022-06-09 02:44:05announced
Publication List
Zinnall U, Milek M, Minia I, Vieira-Vieira CH, Müller S, Mastrobuoni G, Hazapis OG, Del Giudice S, Schwefel D, Bley N, Voigt F, Chao JA, Kempa S, Hüttelmaier S, Selbach M, Landthaler M, HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins. Nat Commun, 13(1):2727(2022) [pubmed]
Keyword List
submitter keyword: HDLBP
Vigilin
RNA-binding protein
KH-domain
endoplasmic reticulum
translation
homo sapiens
QExactive HF
Contact List
Stefan Kempa
contact affiliationIntegrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology at the Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Hannoversche Str. 28, 10115 Berlin, Germany
contact emailstefan.kempa@mdc-berlin.de
lab head
Guido Mastrobuoni
contact affiliationBerlin Institute for Medical Systems Biology at the Max Delbrueck Centrum for Molecular Medicine
contact emailguido.mastrobuoni@mdc-berlin.de
dataset submitter
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