Prusty, Archana Bairavasundaram and Hirmer, Anja and Sierra-Delgado, Julieth Andrea and Huber, Hannes and Guenther, Ulf-Peter and Schlosser, Andreas and Dybkov, Olexandr and Yildirim, Ezgi and Urlaub, Henning and Meyer, Kathrin C. and Jablonka, Sibylle and Erhard, Florian and Fischer, Utz (2024) RNA helicase IGHMBP2 regulates THO complex to ensure cellular mRNA homeostasis. CELL REPORTS, 43 (2): 113802. ISSN 2211-1247
Full text not available from this repository. (Request a copy)Abstract
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 spinal muscular atrophy with respiratory distress type 1 (SMARD1), associates with polysomes and impacts translation of mRNAs containing short, GC -rich, and structured 50 UTRs. The absence of IGHMBP2 causes ribosome stalling at the start codon of target mRNAs, leading to reduced translation efficiency. The main mRNA targets of IGHMBP2-mediated regulation encode for components of the THO complex (THOC), linking IGHMBP2 to mRNA production and nuclear export. Accordingly, failure of IGHMBP2 regulation of THOC causes perturbations of the transcriptome and its encoded proteome, and ablation of THOC subunits phenocopies these changes. Thus, IGHMBP2 is an upstream regulator of THOC. Of note, IGHMBP2-dependent regulation of THOC is also observed in astrocytes derived from patients with SMARD1 disease, suggesting that deregulated mRNA metabolism contributes to SMARD1 etiology and may enable alternative therapeutic avenues.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SPINAL MUSCULAR-ATROPHY; EXPORT; IDENTIFICATION; TRANSLATION; TREX; DNA; TRANSCRIPTION; EXPRESSION; MUTATIONS; S-MU-BP-2 |
| Subjects: | 000 Computer science, information & general works > 004 Computer science 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Informatics and Data Science > Department Computational Life Science > Chair of Computational Immunology (Prof. Dr. Florian Erhard) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 06:39 |
| Last Modified: | 27 Jan 2026 06:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65038 |
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