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

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Item Type:Article
Title:HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins
Creators Name:Zinnall, U., Milek, M., Minia, I., Vieira-Vieira, C.H., Müller, S., Mastrobuoni, G., Hazapis, O.G., Del Giudice, S., Schwefel, D., Bley, N., Voigt, F., Chao, J.A., Kempa, S., Hüttelmaier, S., Selbach, M. and Landthaler, M.
Abstract: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.
Keywords:3' Untranslated Regions, Cell Line, Cytosol, Protein Biosynthesis, Messenger RNA, Signal Recognition Particle, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:13
Number:1
Page Range:2727
Date:18 May 2022
Official Publication:https://doi.org/10.1038/s41467-022-30322-7
PubMed:View item in PubMed

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