PXD044048-2

PXD044048 is an original dataset announced via ProteomeXchange.

Title	RNA helicase Ighmbp2 regulates THO complex to ensure cellular mRNA homeostasis
Description	RNA helicases constitute a large protein family implicated in cellular RNA homeostasis and disease development. Here we show that the RNA helicase Ighmbp2, linked to the neuromuscular disorder SMARD1 associates with polysomes and impacts on translation of cellular mRNAs containing short, GC-rich and highly structured 5’UTRs. Using UV-crosslinking followed by RNAseq and BS3-crosslinking combined with mass spectrometry we were able to localize Ighmbp2 on ribosomes. Absence of Ighmbp2 causes ribosome stalling at the start codon of target mRNAs, leading to their reduced translation efficiency. The main mRNA targets of Ighmbp2-mediated regulation encode for components of the THO complex that links mRNA production and nuclear export. Accordingly, failure of Ighmbp2 regulation of the THO complex causes perturbations of the cellular transcriptome and its encoded proteome. Ablation of essential THO complex subunits phenocopies these perturbations. Thus, Ighmbp2 is an upstream regulator of the THO complex that affects cellular mRNA homeostasis. Of note, Ighmbp2-dependent regulation of the THO complex is also observed in astrocytes derived from SMARD1 patients, suggesting that de-regulated mRNA metabolism contributes to SMARD1 etiology and offers new avenues for developing alternative therapeutics to treating SMARD1.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:29:26.728.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Olexandr Dybkov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-24 14:00:48	ID requested
1	2024-02-14 01:59:40	announced
⏵ 2	2024-10-22 06:29:27	announced	2024-10-22: Updated project metadata.

10.1016/J.CELREP.2024.113802;

submitter keyword: SMUBP-2, THOC, Ighmbp2, SMARD1, mRNA homeostasis,RNA helicase

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Multidisciplinary Sciences, Germany; Bioanalytics, Department of Clinical Chemistry, University Medical Center Göttingen, Germany
contact email	henning.urlaub@mpinat.mpg.de
lab head
Olexandr Dybkov
contact affiliation	Max Planck Institute for Multidisciplinary Sciences
contact email	odybkov@gwdg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD044048

PRIDE project URI

• PRIDE
  1. PXD044048
     1. Label: PRIDE project
     2. Name: RNA helicase Ighmbp2 regulates THO complex to ensure cellular mRNA homeostasis