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Series GSE148258 Query DataSets for GSE148258
Status Public on Feb 04, 2022
Title Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (WT vs HDLBP Ribo-seq + RNA-seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The biological role of RNA-binding proteins (RBPs) in the secretory pathway and their contribution to the recognition and co-translational targeting of ER-localized mRNAs is not well established. In this work we used biochemical, transcriptomic and proteomic approaches to delineate the role of human HDLBP/vigilin. 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 in vivo lung tumor formation. 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 proliferation and tumor progression.
Overall design Translational efficiency in WT vs HDLBP KO HEK293T cells were analyzed by ribosome profiling (ribo-seq) and matching RNA-seq datasets.
Contributor(s) Zinnall U, Milek M, Vieira e Vieira CH, Müller S, Hazapis O, Hüttelmaier S, Selbach M, Landthaler M
Citation(s) 35585045
Submission date Apr 07, 2020
Last update date May 26, 2022
Contact name Markus Landthaler
Organization name MDC Berlin
Department Berlin Institute of Medical Systems Biology
Street address Robert-Roessle Str. 10
City Berlin
ZIP/Postal code 13125
Country Germany
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (12)
GSM4458887 HEK293T ribosome profiling from 293_1
GSM4458888 HEK293T ribosome profiling from 293_2
GSM4458889 HEK293T ribosome profiling from guide1_1
This SubSeries is part of SuperSeries:
GSE148262 HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins
BioProject PRJNA623612
SRA SRP255633

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148258_processed_data_riboseq_psite_coverage.txt.gz 16.4 Mb (ftp)(http) TXT
GSE148258_processed_data_riboseq_te.txt.gz 2.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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