ArticleRNA (New York, N.Y.)2022
A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation.
Article in RNA (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia.British journal of cancer · 2026Article
- EIF4A3-dependent nonsense-mediated decay buffers AML1-ETO9a dosage and modulates outcome in t(8;21) acute myeloid leukemia.Leukemia · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Genomic Expansion and Adaptation in a Parasitoid WaspInsects · 2026Article
- Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis.Scientific reports · 2025Article
- The role of DEAD- and DExH-box RNA helicases in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2024Review
- Translation-coupled mRNA quality control mechanisms.The EMBO journal · 2023Review
- Article
- Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy.Frontiers in oncology · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The DExD/H-box RNA helicase DHX34 is a nonsense-mediated decay (NMD) factor that together with core NMD factors coregulates NMD targets in nematodes and in vertebrates. Here, we show that DHX34 is also associated with the human spliceosomal catalytic C complex. Mapping of DHX34 endogenous binding sites using cross-linking immunoprecipitation (CLIP) revealed that DHX34 is preferentially associated with pre-mRNAs and locates at exon-intron boundaries. Accordingly, we observed that DHX34 regulates a large number of alternative splicing (AS) events in mammalian cells in culture, establishing a dual role for DHX34 in both NMD and pre-mRNA splicing. We previously showed that germline DHX34 mutations associated to familial myelodysplasia (MDS)/acute myeloid leukemia (AML) predisposition abrogate its activity in NMD. Interestingly, we observe now that DHX34 regulates the splicing of pre-mRNAs that have been linked to AML/MDS predisposition. This is consistent with silencing experiments in hematopoietic stem/progenitor cells (HSPCs) showing that loss of DHX34 results in differentiation blockade of both erythroid and myeloid lineages, which is a hallmark of AML development. Altogether, these data unveil new cellular functions of DHX34 and suggest that alterations in the levels and/or activity of DHX34 could contribute to human disease.
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Registered trials
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