A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation
| العنوان: | A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation |
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| المؤلفون: | Nele Hug, Stuart Aitken, Dasa Longman, Michaela Raab, Hannah Armes, Abigail R. Mann, Ana Rio-Machin, Jude Fitzgibbon, Kevin Rouault-Pierre, Javier F. Cáceres |
| المصدر: | Hug, N, Aitken, S, Raab, M, Armes, H, Mann (nee Wilson), A, Rio-machin, A, Fitzgibbon, J, Rouault-Pierre, K & Caceres, J F 2022, ' A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation ', RNA, vol. 28, no. 9, pp. 1224-1238 . https://doi.org/10.1261/rna.079277.122Test |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mammals, RNA, Messenger/genetics, RNA Helicases/genetics, RNA Splicing, Mammals/genetics, Nonsense Mediated mRNA Decay, Leukemia, Myeloid, Acute, Alternative Splicing, Myelodysplastic Syndromes, RNA Precursors, Animals, Humans, Leukemia, Myeloid, Acute/genetics, RNA, Messenger, RNA Precursors/genetics, Myelodysplastic Syndromes/genetics, Molecular Biology, RNA Helicases |
| الوصف: | The DExD/H-box RNA helicase DHX34 is a Nonsense-mediated decay (NMD) factor that together with core NMD factors co-regulates 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 suggests that alterations in the levels and/or activity of DHX34 could contribute to human disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1469-9001 1355-8382 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3bdb207b70cd3ff583ec968ae86f6ecTest https://doi.org/10.1261/rna.079277.122Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e3bdb207b70cd3ff583ec968ae86f6ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14699001 13558382 |
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