Ask about this productRelated genes to: DHX15 Blocking Peptide
- Gene:
- DHX15 NIH gene
- Name:
- DEAH-box helicase 15
- Previous symbol:
- DDX15
- Synonyms:
- HRH2, DBP1, PRP43, PrPp43p, PRPF43
- Chromosome:
- 4p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-05
- Date modifiied:
- 2016-10-05
Related products to: DHX15 Blocking Peptide
Related articles to: DHX15 Blocking Peptide
- Classical acute promyelocytic leukemia (APL) is defined by the presence of the fusion; however, a subset of acute myeloid leukemia (AML) cases presents with morphological and clinical features highly suggestive of APL despite lacking this canonical rearrangement, creating diagnostic and therapeutic dilemmas. We report a 27-year-old woman initially diagnosed with AML characterized by myeloid sarcoma and a predominance of promyelocytes (44%) in the bone marrow. Fluorescence in situ hybridization and RNA sequencing failed to detect , while targeted sequencing revealed mutations in and . Although complete remission was achieved after induction therapy, the response to IA and subsequent CHA chemotherapy regimens was suboptimal. Two years later, the patient relapsed with severe coagulopathy and a marked increase in promyelocytes (71%). Comprehensive genomic re-evaluation at relapse identified a novel fusion and a rare mutation. Notably, transcriptomic analysis demonstrated marked overexpression of and . Based on these molecular findings, treatment with all-trans retinoic acid combined with intermediate-dose cytarabine was initiated, leading to rapid clinical improvement and achievement of complete remission. This case describes a rare AML entity that closely recapitulates the clinical and molecular features of APL in the absence of and suggests that activation of retinoic acid–responsive pathways, potentially mediated by RARA/RXRA overexpression and novel gene fusions, can occur independently of the canonical rearrangement, with important therapeutic implications. - Source: PubMed
Publication date: 2026/04/18
Ma LinaWu Min - Pre-mRNA splicing determines the expressed proteome and is frequently dysregulated in cancer. The tumour-suppressor RBM5 controls an exon network regulating apoptosis, yet its molecular mechanism is elusive. Using in vivo spliceosome capture and cryogenic electron microscopy, we determined structures of precatalytic spliceosomes arrested by RBM5 immediately after U2 snRNP branchpoint recognition. Despite intron diversity, the U2-pre-mRNA duplex, branchpoint adenine, and downstream polypyrimidine tract are well-resolved. RBM5 binds the outer SF3B1 HEAT surface and performs dual functions: First, its helix-loop-helix motif and upstream zinc-finger domain sterically block tri-snRNP and Prp8 docking and prevent progression to pre-B and Bact complexes; Second, its G-patch activates DHX15 and places this DExH-box helicase on the pre-mRNA as it exits SF3B1, poised for branch helix unwinding. DHX15 binding to SF3B1 is facilitated by U2SURP/SR140, which engages SF3B1 near RBM5's helix-loop-helix. Functional assays confirm that disruption of the RBM5 interfaces with either DHX15 or SF3B1 inhibit exon repression. Mutations at these regulatory interfaces are common in cancer genomes and predicted to disrupt its regulation of apoptotic isoforms. Thus, RBM5 acts as a dual-action spliceosome gatekeeper that couples helicase activation with physical stalling to enforce tumour-suppressive alternative splicing programmes. - Source: PubMed
Publication date: 2026/04/08
Zhou Z HongLiu ShihengSu TiantianHuang JeffreyLin Chia-HoBlack DouglasDamianov Andrey - Pre-mRNA splicing determines the expressed proteome and is frequently dysregulated in cancer. The tumour-suppressor RBM5 controls an exon network regulating apoptosis, yet its molecular mechanism is elusive. Using in vivo spliceosome capture and cryogenic electron microscopy, we determined structures of precatalytic spliceosomes arrested by RBM5 immediately after U2 snRNP branchpoint recognition. Despite intron diversity, the U2-pre-mRNA duplex, branchpoint adenine, and downstream polypyrimidine tract are well-resolved. RBM5 binds the outer SF3B1 HEAT surface and performs dual functions: First, its helix-loop-helix motif and upstream zinc-finger domain sterically block tri-snRNP and Prp8 docking and prevent progression to pre-B and B complexes; Second, its G-patch activates DHX15 and places this DExH-box helicase on the pre-mRNA as it exits SF3B1, poised for branch helix unwinding. DHX15 binding to SF3B1 is facilitated by U2SURP/SR140, which engages SF3B1 near RBM5's helix-loop-helix. Functional assays confirm that disruption of the RBM5 interfaces with either DHX15 or SF3B1 inhibit exon repression. Mutations at these regulatory interfaces are common in cancer genomes and predicted to disrupt its regulation of apoptotic isoforms. Thus, RBM5 acts as a dual-action spliceosome gatekeeper that couples helicase activation with physical stalling to enforce tumour-suppressive alternative splicing programmes. - Source: PubMed
Publication date: 2026/03/27
Liu ShihengSu TiantianHuang JeffreyLin Chia-HoBlack Douglas LDamianov AndreyZhou Z Hong - Pre-mRNA splicing is orchestrated by the spliceosome through coordinated RNA and protein rearrangements driven by ATP-dependent RNA helicases. DEAH-box helicases serve as principal motors, controlling catalytic activation, exon ligation, and complex disassembly. Early mechanistic understanding was limited by low-resolution cryo-electron microscopy (cryo-EM) structures, leaving RNA substrate interactions largely inferred from biochemical and genetic studies. Recent high-resolution cryo-EM structures (2021-present) have captured all five spliceosomal DEAH-box helicases-DHX16/Prp2, DHX38/Prp16, DHX8/Prp22, DHX15/Prp43, and DHX35-bound to their RNA targets within distinct spliceosomal states. These structures reveal precise recruitment, substrate recognition, and stage-specific actions. In this review, I integrate these insights into a unified framework, highlighting structural, biochemical, and evolutionary perspectives to guide future investigations of helicase regulation and their role in maintaining the fidelity of eukaryotic RNA splicing. - Source: PubMed
Chen Zhe - Many viral proteins undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates known as viral inclusion bodies (VIBs), which are utilized for genome replication and virion assembly, thus serving as potential targets for antiviral drugs. However, the role of VIBs in viral immune evasion has rarely been explored. In this study, we demonstrated that VP35 protein of type II grass carp reovirus (GCRV-II) formed VIBs through LLPS in cells and in vitro. Moreover, we identified a host interaction partner of GCRV-II VP35, DEAH (Asp-Glu-Ala-His)-box helicase 15 (DHX15), which promoted expression of GCRV-II- or poly(I: C)-induced interferon (IFN) and interferon-stimulated genes (ISGs) via promoting phosphorylation of TBK1 (TANK-binding kinase 1) and stabilizing TBK1 to prevent it from degradation through autophagy pathway. To evade host anti-viral immunity, GCRV-II VP35 sequesters DHX15 from nucleus to the cytoplasm VIBs and degrades DHX15 via lysosomal pathway. Our findings provide a novel immune evasion strategy of GCRV-II, of which VP35 protein recruits DHX15, a positive regulator of host anti-viral immunity, to VIBs and degrades DHX15 via lysosomal pathway, which provides novel insights for the development of anti-viral drugs against GCRV-II infection. - Source: PubMed
Publication date: 2026/02/09
Zhang ChuLv ZhenZeng WeiweiZhang Yong-AnTu Jiagang