HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
18 05 2022
Historique:
received: 22 04 2021
accepted: 13 04 2022
entrez: 18 5 2022
pubmed: 19 5 2022
medline: 21 5 2022
Statut: epublish

Résumé

The biological role of RNA-binding proteins in the secretory pathway is not well established. Here, we describe that human HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs. PAR-CLIP analysis reveals that these transcripts represent high affinity HDLBP substrates and are specifically bound in their coding sequences (CDS), in contrast to CDS/3'UTR-bound cytosolic mRNAs. HDLBP crosslinks strongly to long CU-rich motifs, which frequently reside in CDS of ER-localized mRNAs and result in high affinity multivalent interactions. In addition to HDLBP-ncRNA interactome, quantification of HDLBP-proximal proteome confirms association with components of the translational apparatus and the signal recognition particle. Absence of HDLBP results in decreased translation efficiency of HDLBP target mRNAs, impaired protein synthesis and secretion in model cell lines, as well as decreased tumor growth in a lung cancer mouse model. These results highlight a general function for HDLBP in the translation of ER-localized mRNAs and its relevance for tumor progression.

Identifiants

pubmed: 35585045
doi: 10.1038/s41467-022-30322-7
pii: 10.1038/s41467-022-30322-7
pmc: PMC9117268
doi:

Substances chimiques

3' Untranslated Regions 0
Membrane Proteins 0
RNA, Messenger 0
RNA-Binding Proteins 0
Signal Recognition Particle 0
high density lipoprotein binding protein 147605-06-9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2727

Informations de copyright

© 2022. The Author(s).

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Auteurs

Ulrike Zinnall (U)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Miha Milek (M)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany. miha.milek@bih-charite.de.
National Institute of Chemistry, Ljubljana, Slovenia. miha.milek@bih-charite.de.
Core Unit Bioinformatics, Berlin Institute of Health at Charité, Berlin, Germany. miha.milek@bih-charite.de.

Igor Minia (I)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Carlos H Vieira-Vieira (CH)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Simon Müller (S)

Institute of Molecular Medicine, Medical Faculty, Martin Luther University, Halle, Germany.

Guido Mastrobuoni (G)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Orsalia-Georgia Hazapis (OG)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Simone Del Giudice (S)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

David Schwefel (D)

Charite-Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Berlin, Germany.

Nadine Bley (N)

Institute of Molecular Medicine, Medical Faculty, Martin Luther University, Halle, Germany.

Franka Voigt (F)

Friedrich Miescher Institute for Biomedical Research, 4058, Basel, Switzerland.

Jeffrey A Chao (JA)

Friedrich Miescher Institute for Biomedical Research, 4058, Basel, Switzerland.

Stefan Kempa (S)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.

Stefan Hüttelmaier (S)

Institute of Molecular Medicine, Medical Faculty, Martin Luther University, Halle, Germany.

Matthias Selbach (M)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.
Charite-Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Berlin, Germany.

Markus Landthaler (M)

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany. markus.landthaler@mdc-berlin.de.
IRI Life Sciences, Institute of Biology, Humboldt-Universität zu Berlin, Berlin, Germany. markus.landthaler@mdc-berlin.de.

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Classifications MeSH