Affinage

DHX8

ATP-dependent RNA helicase DHX8 · UniProt Q14562

Round 2 corrected
Length
1220 aa
Mass
139.3 kDa
Annotated
2026-04-28
71 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DHX8 is a DEAH-box ATP-dependent RNA helicase essential for pre-mRNA splicing, functioning at two mechanistically separable steps during the second catalytic reaction and subsequent mRNA release from the spliceosome. In an ATP-independent capacity, DHX8 stabilizes Slu7 association with the spliceosome to promote second-step transesterification, while ATP binding (without hydrolysis) serves a proofreading function that discriminates against aberrant 3′ splice sites; subsequent ATP hydrolysis drives 3′→5′ translocation along the mRNA downstream of the exon–exon junction, disrupting mRNA/U5 snRNP contacts and inducing a Prp8 conformational change to release spliced mRNA (PMID:9524130, PMID:18570877, PMID:40876859). DHX8 forms a complex with cactin and SRRM2 that ensures faithful splicing of pre-mRNAs required for sister chromatid cohesion and genome stability (PMID:28062851). Beyond its nuclear splicing role, DHX8 localizes to the cytoplasmic face of the lysosomal membrane where it interacts with SIDT2 and promotes RNautophagy-dependent RNA degradation, including clearance of pathogenic CAG-repeat RNA (PMID:40842239).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Identification of Prp22 as a DEAH-box protein required for mRNA release from the spliceosome established that an ATP-dependent helicase drives the terminal step of splicing.

    Evidence Genetic screen and mutant analysis in S. cerevisiae with sequence homology to RNA helicases

    PMID:1992352

    Open questions at the time
    • No biochemical confirmation of helicase or ATPase activity
    • Human ortholog not yet identified
  2. 1994 High

    Cloning of the human ortholog HRH1/DHX8 and demonstration of cross-species complementation showed conservation of the mRNA-release function, while revealing a metazoan-specific RS domain mediating SR protein interactions.

    Evidence PCR cloning from HeLa RNA, yeast temperature-sensitive complementation, yeast two-hybrid

    PMID:7935475

    Open questions at the time
    • RS domain function not tested with endogenous human spliceosomes
    • No direct helicase activity demonstrated for the human protein
  3. 1996 High

    Dominant-negative DHX8 mutants demonstrated that its helicase function is required in mammalian cells for spliceosome recycling and proper nuclear export of spliced mRNA.

    Evidence Dominant-negative mutant expression in mammalian cells with in vitro splicing and nuclear export assays

    PMID:8608946

    Open questions at the time
    • Specific spliceosomal targets disrupted by dominant-negative not identified
    • Indirect effect on export versus direct role unclear
  4. 1998 High

    Biochemical reconstitution separated two distinct functions of Prp22: an ATP-independent role in promoting second-step catalysis and an ATP-dependent helicase function for mRNA release, establishing its dual mechanism.

    Evidence Purified recombinant Prp22 in depletion/reconstitution splicing assays with ATPase, RNA unwinding, and Walker A mutagenesis

    PMID:9524130 PMID:9582286

    Open questions at the time
    • Substrate RNA contacts within the spliceosome not mapped
    • Mechanism of ATP-independent second-step promotion not defined
  5. 2002 High

    Systematic mutagenesis of conserved helicase motifs and intragenic suppressor analysis showed that ATP hydrolysis is necessary but not sufficient for mRNA release — translocation/helicase activity is additionally required, indicating a processive remodeling mechanism.

    Evidence Motif II and VI mutagenesis, intragenic suppressor screen, in vitro splicing and unwinding assays

    PMID:11856747 PMID:11861548

    Open questions at the time
    • Spliceosomal RNA–protein contacts disrupted by translocation not identified
    • Structural basis of coupling ATP hydrolysis to translocation unknown
  6. 2005 High

    Quantitative biochemical characterization established Prp22 as a 3′→5′ RNA helicase with nanomolar ssRNA affinity, broad NTPase activity, and a minimum RNA-length requirement for stimulation, defining its enzymology.

    Evidence Filter binding, ATPase with multiple NTPs/dNTPs, RNA unwinding directionality assay with purified protein

    PMID:16008364

    Open questions at the time
    • In vivo NTP specificity not determined
    • Regulation of helicase activity by spliceosomal cofactors unknown
  7. 2008 High

    Site-specific crosslinking revealed that Prp22 engages mRNA downstream of the exon–exon junction after second-step catalysis and disrupts mRNA/U5 snRNP contacts to liberate mRNA, directly mapping its mechanistic target within the spliceosome.

    Evidence Site-specific RNA crosslinking with RNase H protection and distance requirement analysis in yeast splicing extracts

    PMID:18570877

    Open questions at the time
    • Structural details of the mRNA/U5 interface disrupted by Prp22 not resolved
    • Whether the same contacts apply in human spliceosomes not tested
  8. 2012 High

    Crystal structures of the DHX8 C-terminal domain and zebrafish genetic knockouts collectively established structural conservation with related DEAH helicases and revealed that loss of DHX8 causes widespread splicing defects, hematopoietic failure, and mitotic spindle abnormalities.

    Evidence X-ray crystallography (MAD phasing) of human DHX8 CTD; ENU mutagenesis and positional cloning in zebrafish with HeLa knockdown validation

    PMID:22411201 PMID:23096351

    Open questions at the time
    • Full-length DHX8 structure not available
    • Whether mitotic phenotype is secondary to splicing defects not resolved
  9. 2017 High

    Discovery of the DHX8–cactin–SRRM2 complex linked DHX8's splicing function to genome stability by showing that this complex ensures correct splicing of sororin pre-mRNA, which is required for sister chromatid cohesion.

    Evidence Reciprocal co-immunoprecipitation, siRNA depletion, RNA-seq splicing analysis, chromosome segregation assay in human cells

    PMID:28062851

    Open questions at the time
    • Direct versus indirect effect on sororin splicing not distinguished
    • Stoichiometry and assembly pathway of the ternary complex unknown
  10. 2019 High

    Crystal structures of the DHX8 helicase core bound to ADP and to RNA revealed the hook-turn gatekeeper mechanism controlling directional RNA translocation and showed that RNA binding triggers ADP release through conformational flexibility in the DEAH and P-loop motifs.

    Evidence X-ray crystallography of DHX8Δ547 with ADP and poly(A)6, mutagenesis of R620 and hook-turn residues, ATPase/helicase assays

    PMID:31409651

    Open questions at the time
    • Structure in the context of the intact spliceosome not determined
    • Allosteric regulation by spliceosomal cofactors not addressed structurally
  11. 2024 Medium

    Genetic analysis of the C. elegans ortholog MOG-5 demonstrated that DHX8-family helicases proofread 3′ splice site selection cooperatively with DDX41/SACY-1, specifically preventing usage of proximal alternative 3′ splice sites.

    Evidence RNA-seq with CRISPR-Cas9-generated alleles in C. elegans targeting the predicted SACY-1 interaction surface

    PMID:38282418

    Open questions at the time
    • Proofreading mechanism not confirmed in human cells
    • Physical interaction between DHX8 and DDX41 not demonstrated biochemically
    • Structural basis of the proofreading discrimination not known
  12. 2025 High

    Two studies refined the dual mechanism of Prp22/DHX8: ATP binding (not hydrolysis) proofreads 3′ splice sites by inhibiting exon ligation of mutant substrates, Prp22 stabilizes Slu7 during second-step catalysis, and ATP hydrolysis induces a Prp8 conformational change for mRNA release; independently, DHX8 was found at the lysosomal membrane interacting with SIDT2 to regulate RNautophagy-dependent RNA degradation including clearance of pathogenic CAG-repeat RNA.

    Evidence In vitro splicing with ATP-binding vs hydrolysis mutants and spliceosome purification; RNA-binding screen, co-IP, subcellular fractionation, knockdown with RNA degradation and polyQ aggregate assays

    PMID:40842239 PMID:40876859

    Open questions at the time
    • Structural basis of the Prp8 conformational change induced by Prp22 not visualized
    • Mechanism by which DHX8 RNA-binding (without ATPase) promotes RNautophagy is unclear
    • Whether the lysosomal function is independent of or linked to splicing activity is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of DHX8 engagement within the intact human spliceosome, how the lysosomal RNautophagy function relates to the nuclear splicing role, and the full scope of transcripts whose splicing fidelity depends specifically on the DHX8–cactin–SRRM2 complex.
  • No cryo-EM structure of DHX8 within the human C*/P spliceosome
  • Lysosomal versus nuclear function partitioning mechanism unknown
  • Comprehensive identification of DHX8-dependent splice-sensitive transcripts in human cells lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 6 GO:0003723 RNA binding 5 GO:0140098 catalytic activity, acting on RNA 5
Localization
GO:0005634 nucleus 4 GO:0005764 lysosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 10 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 1
Partners
CACTINCWC22PRP45PRP8SIDT2SLU7SRRM2
Complex memberships
DHX8–cactin–SRRM2 complexspliceosome (C*/P complex)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 The yeast PRP22 gene product (ortholog of human DHX8) is required for release of spliced mRNA from the spliceosome. PRP22 protein sequence contains sequence elements characteristic of ATP-dependent RNA helicases (DEAH-box) and a putative RNA-binding motif homologous to bacterial ribosomal protein S1. Genetic screen, yeast mutant analysis, sequence homology Nature High 1992352
1994 HRH1 (human RNA helicase 1, now DHX8) was identified as the human homolog of yeast Prp22. HRH1 can partially rescue temperature-sensitive prp22 yeast mutants. Unlike Prp22, HRH1 contains an RS domain that allows it to interact with SR splicing factors in vitro and in yeast two-hybrid assays, suggesting it is targeted to the spliceosome via this domain. PCR cloning from HeLa RNA, yeast complementation, in vitro binding assay, yeast two-hybrid Molecular and cellular biology High 7935475
1996 Human HRH1 (DHX8) facilitates nuclear export of spliced mRNA by releasing it from the spliceosome. Dominant-negative HRH1 mutants stall on the spliceosome and prevent mRNA release in vitro; expression of dominant-negative HRH1 in mammalian cells inhibits splicing and causes nuclear export of unspliced pre-mRNA due to failure to recycle spliceosome components. The RS domain of HRH1 confers nuclear localization and facilitates spliceosome interaction. Dominant-negative mutant expression, in vitro splicing assay, cell transfection, nuclear export assay Genes & development High 8608946
1998 Purified recombinant yeast Prp22 (DHX8 ortholog) is an RNA-dependent ATPase and an ATP-dependent RNA helicase. Prp22 plays two distinct roles in splicing: (1) an ATP-independent role promoting the second catalytic step (dependent on distance between branchpoint and 3' splice site), and (2) an ATP-requiring function using helicase activity to release mRNA from the spliceosome. Protein purification, in vitro depletion/reconstitution splicing assay, ATPase assay, RNA unwinding assay The EMBO journal High 9524130
1998 Prp22 (DHX8 ortholog) unwinds RNA duplexes in a concentration- and ATP-dependent manner, demonstrating direct RNA structural remodeling activity. mRNA release from the spliceosome is ATP-dependent. Mutation of the ATP phosphate-binding motif (Walker A) eliminates both ATPase and RNA-unwinding activity. Non-hydrolyzable ATP analogs cannot substitute for ATP in the unwinding reaction. Recombinant protein expression, RNA unwinding assay, ATPase assay, site-directed mutagenesis The EMBO journal High 9582286
2002 Dominant-negative Prp22 mutants (D603A, E604A in motif II; Q804A, R808A in motif VI) are defective for ATP hydrolysis and mRNA release but can still promote second-step transesterification. These ATPase-dead mutants bind to spliceosomes and block wild-type Prp22 function in trans. Overexpression causes accumulation of unspliced pre-mRNA in vivo. Mutagenesis, in vitro splicing assay, ATPase assay, in vivo pre-mRNA accumulation analysis The Journal of biological chemistry High 11856747
2002 Intragenic suppressor mutations in Prp22 restore RNA unwinding and mRNA release activity to motif III and DEAH-box mutants. Restoration of mRNA release from the spliceosome is less demanding than unwinding a 25-bp RNA duplex, suggesting the spliceosomal substrate is less stable. ATP hydrolysis by Prp22 is necessary but not sufficient for spliceosome disassembly — helicase activity (RNA translocation) is additionally required. Genetic suppressor screen, in vitro splicing/mRNA release assay, ATPase assay, RNA unwinding assay Genetics High 11861548
2003 Residues in motifs IV (F697) and V (T757, I764, T765) of Prp22 are critical for RNA unwinding and mRNA release. T757 links ATP hydrolysis to RNA cofactor stimulation; T765 makes ATP hydrolysis strictly dependent on RNA. A PRP8 R1753K missense mutation suppresses multiple helicase-deficient prp22 mutations, suggesting Prp22 disrupts an RNA/protein or RNA/RNA interaction in the spliceosome normally stabilized by Prp8. Mutagenesis of 16 conserved residues, in vitro ATPase and helicase assays, genetic suppressor screen, in vivo growth analysis The Journal of biological chemistry High 14688266
2005 Prp22 (DHX8 ortholog) preferentially binds single-stranded RNA over single-stranded DNA or duplex nucleic acids (~20-fold higher affinity). Apparent Kd for poly(A)40 is ~17 nM. Optimal RNA-stimulated ATPase activity requires RNA oligomers ≥20 nt. Prp22 can hydrolyze all common NTPs and dNTPs with comparable efficiencies and unwinds RNA duplexes with 3'→5' directionality. ATP inclusion reduces RNA-binding affinity 3-4 fold. Nitrocellulose filter binding assay, ATPase assay with various NTPs/dNTPs, RNA unwinding directionality assay Biochemistry High 16008364
2008 Prp22 interacts with the mRNA downstream of the exon-exon junction prior to mRNA release, as revealed by site-specific crosslinking and RNase H protection. A conformational rearrangement accompanying the second transesterification step deposits Prp22 on the mRNA downstream of the exon-exon junction. The 3'→5' helicase then disrupts mRNA/U5 snRNP contacts to liberate mRNA. Spliceosome disassembly requires >13 ribonucleotides downstream of the 3' splice site. Site-specific crosslinking, RNase H protection assay, mutational analysis of 3' splice site distance requirements Molecular cell High 18570877
2009 Prp45 (yeast SNW1/SKIP ortholog) affects Prp22 partitioning into spliceosomal complexes. Cwc2-associated spliceosomal complexes from prp45 mutant cells showed decreased stoichiometry of Prp22, suggesting deranged spliceosome interaction. Genetic interactions between prp45 and prp22 alleles implicate Prp45 in facilitating Prp22's role in splicing of non-consensus substrates. Affinity purification of spliceosomal complexes, synthetic lethality screen, in vivo splicing assay Journal of cellular biochemistry Medium 19016306
2012 Crystal structure of the C-terminal domain (CTD) of human Prp22 (DHX8) was determined by MAD phasing. The fold closely resembles yeast Prp43-CTD and shares similarity with winged-helix and ratchet domains of DNA helicase Hel308, suggesting analogous function in dsRNA binding and unwinding. The CTD has a significant impact on ATPase activity of yPrp22 in vitro. Homology modeling of related spliceosomal helicase CTDs reveals conserved positively charged patches representing common RNA-binding surfaces. X-ray crystallography (MAD phasing), homology modeling, in vitro ATPase assay Biological chemistry High 23096351
2012 Loss of dhx8 (zebrafish ortholog of prp22/DHX8) in zebrafish mmy mutants causes splicing defects in many genes including hematopoietic genes, hematopoietic blockage (absence of circulating blood cells by 30 hpf), and cell division defects including disorganized mitotic spindles and multiple spindle poles. DHX8 knockdown in HeLa cells confirmed the cell division phenotype. ENU mutagenesis, positional cloning, in vivo splicing analysis, DHX8 knockdown in HeLa cells, mitotic spindle imaging Developmental dynamics High 22411201
2012 NTR complex (Prp43-Ntr1-Ntr2) can catalyze disassembly of spliceosomes specifically after ATP-dependent action of DEAH-box ATPases Prp2, Prp16, or Prp22, but not before their action or upon their binding to the spliceosome. This links spliceosome disassembly to the functioning of splicing ATPases including Prp22. Affinity purification of spliceosomes arrested at defined stages, in vitro disassembly assay Molecular and cellular biology High 23166295
2013 Drosophila Prp22 (peanuts gene, ortholog of DHX8) is required for chromatin decondensation in germ-line nurse cell nuclei during oogenesis. Loss of peanuts promotes 5-blob chromatin arrest in nurse cell nuclei, and impairs spliceosomal recycling as indicated by accumulation of Prp38 in the nucleoplasm. Other spliceosomal proteins similarly affect nurse cell chromatin morphology. Genetic screen, RNAi, confocal microscopy, immunofluorescence PloS one Medium 24244416
2017 Human DHX8 physically and functionally interacts with cactin and SRRM2. Depletion of cactin reduces splicing efficiency of thousands of pre-mRNAs and leads to incomplete splicing of sororin (CDCA5) pre-mRNA, causing premature sister chromatid separation. Cellular complexes comprising cactin, DHX8, and SRRM2 sustain precise chromosome segregation and genome stability by allowing faithful splicing of specific pre-mRNAs. Co-immunoprecipitation, siRNA depletion, RNA-seq splicing analysis, chromosome segregation assay Journal of cell science High 28062851
2019 Crystal structures of the catalytically active helicase core of human DHX8 (DHX8Δ547) were determined bound to ADP and bound to poly(A)6 single-strand RNA. DHX8 has in vitro binding preference for adenine-rich RNA. RNA binding triggers ADP release through significant conformational flexibility in the DEAH-, P-loop, and hook-turn motifs. R620 and both the hook-turn and hook-loop regions are essential for DHX8 helicase activity. The hook-turn acts as a gatekeeper to regulate directional movement of the 3' end of RNA through the RNA-binding channel. X-ray crystallography, biochemical ATPase/helicase assays, site-directed mutagenesis The Biochemical journal High 31409651
2024 C. elegans MOG-5 (Prp22/DHX8 ortholog) and SACY-1 (DDX41 ortholog) have overlapping roles in proofreading 3' splice site selection, specifically preventing usage of proximal (upstream) adjacent 3' splice sites within ≤18 nt pairs. Alleles of mog-5 in the region predicted to interact with SACY-1 based on human C* spliceosome structure promote proximal alternative 3'ss usage, similar to SACY-1 depletion. RNA-seq transcriptomic analysis, CRISPR-Cas9 allele generation, genetic analysis RNA Medium 38282418
2025 DHX8 was identified as a binding partner of consecutive guanine sequences in RNA. DHX8 interacts with SIDT2 (a lysosomal membrane protein) and is partially localized to the cytoplasmic side of the lysosomal membrane. DHX8 regulates intracellular RNA degradation via SIDT2-dependent RNautophagy (not macroautophagy). RNA binding, but not ATPase activity, of DHX8 is important for regulating RNA degradation. DHX8 also contributes to clearance of pathogenic CAG repeat mRNA and RNA foci, reducing levels of expanded polyQ protein aggregates. RNA-protein binding screen, co-immunoprecipitation, subcellular fractionation, knockdown/overexpression with RNA degradation assays, polyQ aggregate quantification Nucleic acids research High 40842239
2025 Prp22 promotes exon ligation by stabilizing Slu7's association with the spliceosome prior to exon ligation (ATP-independent role). ATP binding (not hydrolysis) by Prp22 inhibits exon ligation of 3' splice site mutant pre-mRNAs, serving a proofreading function. After exon ligation, Prp22-mediated ATP hydrolysis facilitates dissociation of both Slu7 and mRNA from the spliceosome. Prp22-driven ATP hydrolysis induces a conformational change in Prp8 that disrupts interdomain interactions to enable mRNA release. Prp22 and Cwc22 remain associated with the released mRNA, whereas Slu7 and Fyv6 dissociate independently. In vitro splicing assay with ATPase mutants, spliceosome purification, protein association analysis Nucleic acids research High 40876859

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2005 Nucleolar proteome dynamics. Nature 934 15635413
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2014 A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 325 25036637
2012 Dynamic protein-protein interaction wiring of the human spliceosome. Molecular cell 318 22365833
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
1991 Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes. Nature 318 1992352
2002 Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA (New York, N.Y.) 301 11991638
2005 Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. Nature methods 243 16094384
1998 Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA splicing. The EMBO journal 205 9524130
2017 Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature 204 28076346
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2012 NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function. Molecular cell 174 23022380
2013 Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. Journal of cell science 172 23345399
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
1998 The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. The EMBO journal 140 9582286
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2008 A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Molecular cell 109 18570877
1996 A human RNA helicase-like protein, HRH1, facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome. Genes & development 88 8608946
1994 Identification of a putative RNA helicase (HRH1), a human homolog of yeast Prp22. Molecular and cellular biology 65 7935475
2005 Characterization of the NTPase, RNA-binding, and RNA helicase activities of the DEAH-box splicing factor Prp22. Biochemistry 63 16008364
2000 The hermaphrodite sperm/oocyte switch requires the Caenorhabditis elegans homologs of PRP2 and PRP22. Proceedings of the National Academy of Sciences of the United States of America 61 10737793
2003 Motifs IV and V in the DEAH box splicing factor Prp22 are important for RNA unwinding, and helicase-defective Prp22 mutants are suppressed by Prp8. The Journal of biological chemistry 52 14688266
2002 Characterization of dominant-negative mutants of the DEAH-box splicing factors Prp22 and Prp16. The Journal of biological chemistry 50 11856747
2012 Link of NTR-mediated spliceosome disassembly with DEAH-box ATPases Prp2, Prp16, and Prp22. Molecular and cellular biology 35 23166295
2009 Prp45 affects Prp22 partition in spliceosomal complexes and splicing efficiency of non-consensus substrates. Journal of cellular biochemistry 31 19016306
2005 Dual role of histamine in modulation of Leydig cell steroidogenesis via HRH1 and HRH2 receptor subtypes. Biology of reproduction 30 15917347
2012 Structural analysis of the C-terminal domain of the spliceosomal helicase Prp22. Biological chemistry 25 23096351
2012 Incomplete splicing, cell division defects, and hematopoietic blockage in dhx8 mutant zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 22 22411201
2002 ATP-dependent remodeling of the spliceosome: intragenic suppressors of release-defective mutants of Saccharomyces cerevisiae Prp22. Genetics 22 11861548
2018 Functional G-Protein-Coupled Receptor (GPCR) Synthesis: The Pharmacological Analysis of Human Histamine H1 Receptor (HRH1) Synthesized by a Wheat Germ Cell-Free Protein Synthesis System Combined with Asolectin Glycerosomes. Frontiers in pharmacology 21 29467651
2017 Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion. Journal of cell science 21 28062851
2013 Variability in histamine receptor genes HRH1, HRH2 and HRH4 in patients with hypersensitivity to NSAIDs. Pharmacogenomics 19 24236486
2019 Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release. The Biochemical journal 17 31409651
2019 Comparative Genomics of Thiohalobacter thiocyanaticus HRh1T and Guyparkeria sp. SCN-R1, Halophilic Chemolithoautotrophic Sulfur-Oxidizing Gammaproteobacteria Capable of Using Thiocyanate as Energy Source. Frontiers in microbiology 11 31118923
2019 Human H1 receptor (HRH1) gene polymorphism is associated with the severity of side effects after desloratadine treatment in Chinese patients with chronic spontaneous uticaria. The pharmacogenomics journal 11 31406237
2018 A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families with hereditary breast and ovarian cancer syndrome. Breast cancer research and treatment 10 30191368
2013 Prp22 and spliceosome components regulate chromatin dynamics in germ-line polyploid cells. PloS one 8 24244416
2003 Analysis of the role of Bphs/Hrh1 in the genetic control of responsiveness to pertussis toxin. Infection and immunity 8 12595443
2024 Spliceosomal helicases DDX41/SACY-1 and PRP22/MOG-5 both contribute to proofreading against proximal 3' splice site usage. RNA (New York, N.Y.) 7 38282418
2023 Integrative analysis of small non-coding RNAs predicts a piRNA/miRNA-CCND1/BRAF/HRH1/ATXN3 regulatory circuit that drives oncogenesis in glioblastoma. Molecular omics 7 36688618
2023 The Roles of Histamine Receptor 1 (hrh1) in Neurotransmitter System Regulation, Behavior, and Neurogenesis in Zebrafish. Molecular neurobiology 7 37474883
2024 The Anti-Obesogenic Effects of Muscadine Grapes through Ciliary Neurotrophic Factor Receptor (Cntfr) and Histamine Receptor H1 (Hrh1) Genes in 3T3-L1 Differentiated Mouse Cells. Nutrients 5 38931172
2025 MRGPRX2 Mediates Mast Cell-Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/HRH1/TRPV1 Signaling Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 40600649
2025 DHX8 regulates degradation of RNA by RNautophagy. Nucleic acids research 2 40842239
2025 New mechanistic insights into Prp22-mediated exon ligation and mRNA release. Nucleic acids research 2 40876859
2025 Gut microbiota-derived histamine exacerbates psoriasis by promoting γδT17 cell differentiation via the Hrh1/Wnt Axis. International immunopharmacology 2 41014774
2025 HRH1-targeting mAb: a precision therapeutic strategy for Glioblastoma. Oncogene 2 41125791
2024 Macrophage Scavenger Receptor 1 attenuates ischemic white matter injury via HRH1-mediated microglial phagocytosis. Neuroscience letters 2 39214333
2024 Identification of HRH1 as an alternative receptor for SARS-CoV-2: insights from viral inhibition by repurposable antihistamines. mBio 1 39037273
2019 Effect of the Fexofenadine on the expression of HRH-1 and HRH-4 receptor in Peripheral Blood Mononuclear Cell isolated from children with diagnosed allergy - in vitro study Short communication. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 1 30742585
2026 DHX8 Plays a Critical Role in Larval Development in Lepidopteran Bombyx mori. Insects 0 41898898
2025 Sensitive detection of pertussis toxin in acellular pertussis vaccines using HRH1-mediated calcium signaling. Vaccine 0 40158234
2025 The Histamine-Associated Inflammatory Landscape of Endometriosis: Molecular Profiling of HDC, HRH1-HRH4, and Cytokines Across Lesion Subtypes. International journal of molecular sciences 0 41516088
2021 High Expression of Histamine Receptor, HRH1, Reduces Immunotherapy Response. Cancer discovery 0 34893496