Affinage

DHX36

ATP-dependent DNA/RNA helicase DHX36 · UniProt Q9H2U1

Length
1008 aa
Mass
114.8 kDa
Annotated
2026-06-09
83 papers in source corpus 45 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DHX36 (RHAU) is a DEAH-box helicase that serves as the principal cellular activity for resolving parallel G-quadruplex (G4) structures in both DNA and RNA, coupling structure-specific recognition to ATP-driven unfolding to control gene expression across transcription, translation, mRNA decay, and innate immunity (PMID:16150737, PMID:20472641). Substrate selectivity is conferred by an N-terminal DHX36-specific motif (RSM/DSM) that folds into a G4-induced α-helix capping a terminal guanine tetrad through three-anchor electrostatic contacts, with the RecA2 and OB-fold domains completing recognition and translocation (PMID:26195789, PMID:29899445, PMID:40833853); the helicase loads onto a 3' single-stranded tail and translocates 3'→5', and net G4 unfolding requires ATP hydrolysis rather than nucleotide binding alone, with binding/capture and disruption being mechanistically separable steps (PMID:28069994, PMID:29269411, PMID:33857359). In the cytoplasm DHX36 binds G4-forming sequences across thousands of mRNAs, unwinding 5'UTR rG4s to license translation and promoting 3'UTR remodeling that drives YTHDF1/m6A-dependent decay, thereby exerting opposing dual post-transcriptional control on individual transcripts (PMID:26489465, PMID:31160600, PMID:39543097). In the nucleus it resolves promoter and transcription-associated G4-DNA to activate gene expression and maintain genomic integrity, coordinating with REV1 during replication of G4-containing DNA (PMID:37632696, PMID:39366945, PMID:42258547). DHX36 also governs antiviral signaling, partnering with TRIF/DDX1/DDX21 and with PKR in a dsRNA-dependent manner and acting as a rheostat that restrains constitutive PKR- and RIG-I-driven type I interferon responses by surveilling RNA structure (PMID:21703541, PMID:24651521, PMID:42213826). Through these activities DHX36 is essential in mice for hematopoiesis, cardiac development and conduction-system formation, muscle satellite cell expansion, spermatogenesis, and oocyte rRNA processing and female fertility (PMID:22422825, PMID:34413292, PMID:39366945, PMID:40023726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Established the first molecular function for RHAU as an mRNA-destabilizing factor, linking it to deadenylation machinery before its G4 activity was known.

    Evidence Co-IP with PARN/exosome, ATPase-dead mutant, and ARE-mRNA decay assays

    PMID:14731398

    Open questions at the time
    • Did not connect decay activity to G4 structures
    • Mechanism of substrate selection via HuR/NFAR1 not fully resolved
  2. 2005 High

    Identified DHX36 as the dominant cellular G4-DNA resolvase, defining its signature biochemical activity.

    Evidence G4-DNA affinity purification, mass spectrometry, recombinant resolvase assay, and immunodepletion of HeLa lysates

    PMID:16150737

    Open questions at the time
    • Did not define the structural basis of G4 recognition
    • Residual resolving activity after depletion implies additional G4 helicases
  3. 2010 High

    Localized G4 recognition specificity to the N-terminal RSM, separating substrate recognition from the helicase core.

    Evidence Domain deletion/mutagenesis with in vitro binding and resolvase assays, conserved in the Drosophila ortholog

    PMID:20472641

    Open questions at the time
    • Atomic basis of RSM-G4 contact not yet resolved
    • Did not address DNA vs RNA discrimination
  4. 2011 High

    Connected DHX36 to telomerase biology and to innate immune dsRNA sensing, broadening its functional scope beyond mRNA decay.

    Evidence RIP-chip and in vitro binding for TERC/hTR G4; poly I:C affinity purification, Co-IP, domain mapping, and shRNA knockdown for the TRIF/DDX1/DDX21 complex

    PMID:21149580 PMID:21703541 PMID:21846770

    Open questions at the time
    • Whether helicase activity is required for telomerase assembly was not resolved here
    • How DHX36 is recruited into the dsRNA-sensing complex remained partly open
  5. 2012 High

    Demonstrated DHX36 is essential in vivo and that its developmental requirement reflects G4 resolvase activity on target gene promoters.

    Evidence Conditional knockout mouse (Vav1-Cre) with hematopoietic phenotyping and transcriptomics; in vitro hTR helicase assay with telomere length measurement

    PMID:22238380 PMID:22422825

    Open questions at the time
    • Direct in vivo demonstration that promoter G4 resolution drives the transcriptome changes was correlative
    • Embryonic lethality precluded analysis of germline-null adult phenotypes
  6. 2013 High

    Extended DHX36 function to post-transcriptional silencing, placing it within miRNA/Ago2-dependent translational repression and dendritic RNA localization.

    Evidence RNA-IP, loss-of-function, dendritic spine morphometry (pre-miR-134); RIP, siRNA, and Ago2 co-depletion (PITX1 3'UTR G4)

    PMID:23651854 PMID:24369427

    Open questions at the time
    • Mechanism coupling G4 resolution to Ago2 recruitment not dissected
    • Whether helicase ATPase activity is required for the silencing role unclear
  7. 2014 High

    Defined a dsRNA-dependent partnership with PKR and a positive role in antiviral stress granule formation and interferon production.

    Evidence Reciprocal dsRNA-dependent Co-IP, DHX36 KO MEF cells, IFN and viral infection assays

    PMID:24651521

    Open questions at the time
    • Apparent positive role here later reconciled with a restraining rheostat function
    • Direct effect of helicase activity on PKR autophosphorylation not structurally resolved
  8. 2015 High

    Provided the structural mechanism of parallel-G4 specificity and showed in vivo that dual UTR regulation and G4 promoter binding underlie cardiac and germ-cell development.

    Evidence NMR peptide-G4 structure; cardiac and germ-cell conditional KO mice with RIP, translation/decay assays, and c-kit promoter pulldown

    PMID:25611385 PMID:26195789 PMID:26489465

    Open questions at the time
    • c-kit promoter regulation rests on a single lab
    • How a single protein selects translation-promoting versus decay-promoting outcomes on the same mRNA not mechanistically defined
  9. 2016 High

    Resolved the nucleotide-state logic of G4 handling — binding stabilizes, hydrolysis destabilizes — and mapped additional roles in stress granules, p53 pre-mRNA processing, and nuclear localization.

    Evidence Single-molecule magnetic tweezers with nucleotide-state control and domain mutants; SG localization mapping; pre-mRNA 3'-end processing assays; immunofluorescence/fractionation

    PMID:18279852 PMID:18854321 PMID:26740632 PMID:27940037 PMID:28069994

    Open questions at the time
    • Distinction between stabilizing and destabilizing modes in vivo not established
    • Functional significance of nucleolar cap relocalization unresolved
  10. 2017 High

    Established the translocation-based unwinding mechanism, showing DHX36 loads on a 3' tail and moves 3'→5' to disrupt G4 far more efficiently than duplex DNA.

    Evidence In vitro kinetic assays with G4 substrates and PEG-linker translocation blocks

    PMID:29269411

    Open questions at the time
    • Kinetics performed on model substrates, not endogenous chromatin G4
    • Did not address RNA G4 mechanistic differences
  11. 2018 High

    Delivered atomic-resolution mechanism: the DSM-induced α-helix plus OB-fold and RecA2 pocket capture parallel G4 and drive stepwise tail-pulling unfolding, and revealed RNA-vs-DNA mechanistic asymmetry and a translation-licensing role in cells.

    Evidence X-ray co-crystallography of multiple states plus smFRET (bovine and Drosophila); ribosome profiling with DHX36/DHX9 depletion and PAR-CLIP

    PMID:29429875 PMID:29899445 PMID:30591072

    Open questions at the time
    • Structures captured discrete states rather than full processive cycle
    • Functional overlap and division of labor with DHX9 not fully delineated
  12. 2019 High

    Defined the transcriptome-wide rG4 regulon and the asymmetric RNA-G4 mechanism, showing DHX36 binds >4500 mRNAs and renders rG4 transcripts translationally competent while restraining stress granules and PKR.

    Evidence PAR-CLIP, KO cell lines with polysome/ribosome profiling, SG imaging; smFRET with mutagenesis revealing ATP-independent RNA-G4 unfolding/refolding

    PMID:31015431 PMID:31160600

    Open questions at the time
    • Why RNA-G4 unfolding is ATP-independent while DNA-G4 unfolding requires hydrolysis not fully explained
    • Direct in vivo demonstration of refolding role lacking
  13. 2020 High

    Dissected the contributions of auxiliary domains (DSM, OB-fold, β-hairpin) to recognition versus remodeling and showed the DSM accelerates G4 capture (on-rate) without affecting the disruption step.

    Evidence Mouse DHX36-ADP crystal structure with mutagenesis and helicase assays; kinetic binding assays with DSM truncation; lncRNA GSEC inhibition assays

    PMID:27797375 PMID:32087197 PMID:33857359

    Open questions at the time
    • How separable capture and disruption steps are coordinated during processive cycles unclear
    • Physiological scope of lncRNA-mediated inhibition not established
  14. 2021 Medium

    Established DHX36 as broadly essential for adult tissue regeneration and identified specific 5'UTR rG4 targets and a lncRNA/EIF3B co-factor axis, while linking it to repeat RNA translation.

    Evidence Inducible satellite-cell and cardiomyocyte conditional KO mice with PAR-CLIP, polysome profiling, RIP, and target validation (Gnai2, Yap1/Hexim1, Anp32e via Lockd); C9orf72 RAN translation reporters

    PMID:33199370 PMID:34174288 PMID:34413292 PMID:35675771

    Open questions at the time
    • Generality of the Lockd/EIF3B translation-activating complex across cell types unknown
    • Pathological consequences of DHX36-driven repeat RAN translation in disease not established in vivo
  15. 2022 Medium

    Reinforced the 5'UTR rG4 translation-derepression paradigm at additional immune-relevant targets and showed nuclear DHX36 protects genomic integrity from transcription-associated G4-DNA.

    Evidence rG4-specific cellular probes with KD/KO and translation assays (ADAR1); depletion with γH2AX, G4 co-localization, and G4-binding-mutant rescue

    PMID:36300875 PMID:37632696

    Open questions at the time
    • Whether ADAR1 derepression alters editing output not addressed
    • Partial rescue by G4-binding mutants implies G4-independent contributions to genome maintenance
  16. 2024 High

    Unified the dual UTR phenomenon mechanistically by showing transcript-wide structural remodeling that increases 3'UTR accessibility and recruits YTHDF1 to m6A sites for decay, and tied promoter-G4 resolution to cardiac conduction-system morphogenesis.

    Evidence RNA structurome-seq with DHX36 depletion, m6A mapping, YTHDF1 CLIP, KO cells; cardiac conditional KO with snRNA-seq and snATAC-seq

    PMID:39366945 PMID:39543097

    Open questions at the time
    • How DHX36 binding at one site propagates structure changes across an entire transcript not mechanistically defined
    • Direct demonstration that promoter G4 resolution causes the conduction phenotype remains correlative
  17. 2025 High

    Recast DHX36 as a rheostat for innate immunity and rRNA biogenesis, defined a REV1 replication-coupling partnership and viral antagonism, and provided cryo-EM-based DNA/RNA discrimination logic.

    Evidence KO cells with PKR/SG/ISG/RIG-I and viral replicon assays; oocyte conditional KO with rRNA processing and rescue; REV1 Co-IP/domain mapping; cryo-EM of RNA/DNA G4 complexes with smFRET; PCV3 ubiquitination/degradation assays; StAR 3'UTR G4 KD with hormonal readout

    PMID:39862752 PMID:40023726 PMID:40833853 PMID:40985767 PMID:41354365 PMID:42213826 PMID:42258547

    Open questions at the time
    • How dsRNA exposure mechanistically lowers DHX36 activity to license immune activation not fully defined
    • Whether RecA2-mediated DNA/RNA discrimination dictates the distinct in-cell DNA versus RNA roles untested in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single DHX36 molecule selects between opposing fates on the same transcript (5'UTR translation activation versus 3'UTR-driven decay) and how its activity is dynamically tuned across nuclear, cytoplasmic, and immune contexts.
  • No model integrates compartment-specific cofactors, post-translational regulation, and substrate features into a predictive logic
  • Whether the nucleotide-state stabilize/destabilize switch operates the same way on cellular G4-DNA and G4-RNA is untested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 6 GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 5 GO:0003677 DNA binding 4 GO:0140657 ATP-dependent activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 2
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
DDX1DDX21EIF3BPARNPKRREV1TRIFYTHDF1
Complex memberships
DHX36-PKR complexTRIF/DDX1/DDX21 dsRNA-sensing complextelomerase holoenzyme (via TERC/hTR)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 DHX36 (RHAU) is the major source of tetramolecular G4-DNA resolving activity in HeLa cell lysates. Recombinant DHX36 expressed in E. coli displayed robust, NTP-dependent G4-DNA resolving activity, and immunodepletion of DHX36 from lysates removed ~77% of the enzyme and reduced G4-DNA resolving activity to ~46% of control. G4-DNA affinity purification, mass spectrometry, in vitro G4-resolvase assay with recombinant protein, immunodepletion The Journal of biological chemistry High 16150737
2004 RHAU (DHX36) physically interacts with the deadenylase PARN and the human exosome, enhancing deadenylation and decay of ARE-containing mRNAs (ARE-uPA). ATPase activity of RHAU is essential for its mRNA-destabilizing function. RHAU recognizes ARE-uPA mRNA via RNA-dependent interaction with AUBPs HuR and NFAR1. Co-immunoprecipitation, mRNA decay assays, ATPase-dead mutant analysis, RNA-protein interaction assays Molecular cell High 14731398
2010 The amino-terminal RHAU-specific motif (RSM) of DHX36 is the major affinity and specificity determinant for G4-RNA binding and G4-resolvase activity. Deletion of the RSM abolishes G4 binding and resolution. The Drosophila ortholog CG9323 also requires the RSM for G4-RNA recognition and resolution. Domain deletion/mutagenesis, in vitro G4-binding and resolvase assays, cross-species comparison Nucleic acids research High 20472641
2011 DDX1, DDX21, and DHX36 form a complex with adaptor molecule TRIF to sense cytosolic dsRNA in myeloid dendritic cells. DHX36 binds the TIR domain of TRIF via its HA2-DUF domain. Knockdown of DHX36 or TRIF blocked type I IFN and cytokine responses to poly I:C, influenza A virus, and reovirus. Poly I:C affinity purification, Co-IP, shRNA knockdown, cytokine/IFN response assays, domain mapping Immunity High 21703541
2011 DHX36 binds an intramolecular G4-RNA structure in the 5' region of the telomerase RNA TERC in vivo and in vitro. RHAU associates with the telomerase holoenzyme via the 5' region of TERC. Binding requires the intact G4 structure. RIP-chip (RNA immunoprecipitation-microarray), in vitro binding assays, bioinformatics Nucleic acids research High 21846770
2012 RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA (hTR) 5' region, promoting formation of the P1 helix template boundary required for reverse transcription. RHAU knockdown reduced average telomere length. In vitro helicase assay, RNA structural analysis, siRNA knockdown, telomere length measurement Nucleic acids research High 22238380
2012 RHAU is essential for mouse hematopoiesis; germ-line deletion causes embryonic lethality, and hematopoietic-specific deletion causes hemolytic anemia and differentiation block at the proerythroblast stage due to a proliferation defect. Deregulated genes in knockout proerythroblasts are enriched for G4 motifs in their promoters, suggesting G4 resolvase activity underlies the phenotype. Conditional knockout mouse (Vav1-Cre), hematopoietic phenotyping, transcriptome analysis Blood High 22422825
2013 DHX36 directly associates with the terminal loop of precursor-miR-134 (pre-miR-134) and mediates its dendritic localization in hippocampal neurons. DHX36 function is required for miR-134-dependent inhibition of target gene expression and control of dendritic spine size. RNA immunoprecipitation, in situ localization, DHX36 loss-of-function, dendritic spine morphometry, target gene expression assays Genes & development High 23651854
2013 RHAU (DHX36) binds G4 structures in the 3' UTR of PITX1 mRNA. RHAU knockdown increases PITX1 protein levels with only marginal mRNA changes, indicating translational repression. This regulation requires Argonaute-2 and is non-additive with Dicer knockdown, placing RHAU in microRNA-mediated translational silencing. RNA co-immunoprecipitation, siRNA knockdown, Western blot, Ago2 co-depletion Nucleic acids research Medium 24369427
2014 DHX36 forms a complex with PKR (dsRNA-dependent protein kinase) in a dsRNA-dependent manner and facilitates dsRNA binding and phosphorylation (activation) of PKR through its ATPase/helicase activity, promoting antiviral stress granule (avSG) formation and RIG-I signaling. DHX36 KO MEF cells show defective IFN production and increased susceptibility to RNA virus infection. Co-immunoprecipitation (dsRNA-dependent), DHX36 knockout inducible MEF cells, IFN production assay, viral infection assay PLoS pathogens High 24651521
2015 An 18-amino-acid N-terminal G-quadruplex-binding domain of RHAU folds upon G4 binding and covers a terminal guanine tetrad using three-anchor-point electrostatic interactions between positively charged residues and phosphate groups, conferring parallel G4 specificity. NMR solution structure of peptide-G4 complex, binding assays Proceedings of the National Academy of Sciences of the United States of America High 26195789
2015 Cardiac deletion of Rhau causes heart defects and embryonic lethality. Nkx2-5 mRNA is a RHAU target: RHAU binds the 5' UTR G4 to promote protein translation and the 3' UTR ARE to facilitate mRNA decay, providing dual post-transcriptional regulation of Nkx2-5 in heart development. Cardiac-specific conditional knockout mouse, gene expression profiling, RNA co-IP, mRNA stability and translation assays Cell reports High 26489465
2015 RHAU is essential for spermatogonia differentiation; germ-cell-specific knockout increases G4 DNA accumulation and reduces expression of c-kit (a differentiation gene with G4 motifs in its promoter). RHAU directly binds to G4 structures in the c-kit promoter to activate c-kit expression. Germ-cell-specific conditional knockout mouse, G4 probe staining, chromatin pull-down, c-kit expression analysis Cell death & disease Medium 25611385
2016 DHX36 binds the G4 structure near the polyadenylation site of p53 pre-mRNA and is necessary to maintain p53 pre-mRNA 3'-end processing following UV-induced DNA damage. G4 mutation or G4-stabilizing ligands impair this processing. RNA binding assays, siRNA knockdown, pre-mRNA 3'-end processing assays, G4 mutation and pharmacological G4 stabilization Journal of molecular biology Medium 27940037
2016 RHAU is recruited to stress granules via a newly identified N-terminal RNA-binding domain that is both necessary and sufficient for SG localization. ATPase activity of RHAU modulates RNA interaction and regulates protein retention in SGs. Live imaging, domain deletion mapping, ATPase-dead mutant, stress granule marker co-localization The Journal of biological chemistry Medium 18854321
2016 RHAU stabilizes G4 DNA in nucleotide-free, AMP-PNP-bound, and ADP-bound states, but destabilizes G4 upon ATP hydrolysis. Both the 3' ssDNA tail and the RSM domain are dispensable for G4 stabilization but required for G4 destabilization, demonstrating distinct functional requirements for binding versus unfolding. Single-molecule magnetic tweezers with Drosophila RHAU, nucleotide-state manipulation, RSM and tail mutants Nucleic acids research High 28069994
2008 RHAU is localized predominantly in the nucleus under normal conditions; transcriptional arrest redistributes it to nucleolar caps where it co-localizes with RNA helicases p68 and p72. Knockdown affects steady-state mRNA levels without altering mRNA half-lives for most affected transcripts, suggesting a transcriptional rather than mRNA decay role in the nucleus. Immunofluorescence, subcellular fractionation, transcriptional inhibitor treatment, microarray analysis with actinomycin D chase Experimental cell research Medium 18279852
2018 Co-crystal structure of bovine DHX36 bound to a parallel G4-DNA with a 3' ssDNA tail reveals that the N-terminal DHX36-specific motif (DSM) folds into a DNA-binding-induced α-helix that, together with an OB-fold-like subdomain, selectively binds parallel G4s. Comparison of unliganded, ATP-analogue-bound, and G4-bound structures plus smFRET analyses suggests G4 binding induces helicase core rearrangements that drive unfolding by pulling the ssDNA tail one residue at a time. X-ray co-crystallography (multiple structures), single-molecule FRET (smFRET) Nature High 29899445
2018 Crystal structures of Drosophila DHX36 (DmDHX36) in complex with RNA and various DNAs reveal that positively charged residues in RecA2 and OB-like domains form a structural pocket at the nucleic acid entrance where G4 DNA is tightly bound and partially destabilized, followed by complete unfolding via 3'–5' translocation. X-ray crystallography, SAXS, molecular dynamics simulation, single-molecule fluorescence, DNA binding assays Structure High 29429875
2018 Depletion of DHX36 or DHX9 promotes translation of rG4-associated upstream open reading frames (uORFs) while reducing translation of main ORFs of rG4-containing mRNAs including proto-oncogenes and transcription factors. DHX9 mediates this through direct physical interaction with rG4 substrates. Ribosome profiling (transcriptome-wide), siRNA depletion of DHX36 and DHX9, transcriptome-wide DHX9 binding site mapping (PAR-CLIP) Genome biology High 30591072
2019 DHX36 binds G-rich and G4-forming sequences on >4500 mRNAs genome-wide. DHX36 KO increases target mRNA abundance but decreases ribosome occupancy and protein output, indicating these mRNAs become translationally incompetent. DHX36 KO increases stress granule formation and PKR phosphorylation. PAR-CLIP (global RNA binding mapping), DHX36 knockout cell lines, polysome profiling, ribosome profiling, stress granule imaging Nature communications High 31160600
2019 DHX36 displays ATP-independent unfolding of G4-RNA followed by ATP-dependent refolding, a highly asymmetric pattern distinct from its G4-DNA activity. ATP-dependent activity arises from the RNA tail rather than the G4 itself. Mutations perturbing G4 contact cause rapid protein dissociation upon ATP hydrolysis; mutations interfering with RNA tail binding cause dysregulated activity. Single-molecule FRET, site-directed mutagenesis, in vitro helicase assays Nature communications High 31015431
2017 DHX36 disrupts DNA G4s via a translocation-based helicase mechanism: it loads onto a 3' ssDNA extension and translocates 3'–5' toward the G4. Disruption rates depend on G4 length under saturating conditions (kcat) but not subsaturating (kcat/K), and a polyethylene glycol linker blocking translocation abolishes activity. DHX36 unwinds G4s far more efficiently than dsDNA of comparable intrinsic lifetime. In vitro kinetic assays with tetramolecular and unimolecular G4 substrates, linker-block experiments The Journal of biological chemistry High 29269411
2011 DHX36 (RHAU) binds the G-quadruplex-forming 5' guanosine tracts of human telomerase RNA (hTR) via its N-terminal accessory domain (not the helicase domain). G4 mutations in hTR substantially reduce mature hTR accumulation and telomere maintenance, suggesting G4 formation protects immature hTR from degradation. Co-immunoprecipitation, domain mapping, hTR guanosine tract substitution mutants, telomere maintenance assays Molecular and cellular biology Medium 21149580
2011 DHX36 facilitates TNAP transcription by binding the MS-275 response element in the TNAP promoter. DHX36 physically interacts with HDAC1 and HDAC4, and MS-275 (HDAC inhibitor) decreases this HDAC–DHX36 interaction, relieving transcriptional repression of TNAP. DNA affinity precipitation assay, co-immunoprecipitation, TNAP promoter deletion reporter assays, HDAC inhibitor treatment Journal of bone and mineral research Medium 21590736
2016 RHAU (DHX36) interacts with the 3' adenosine-rich region of long non-coding RNA BC200 (BCYRN1) via a C-terminal region specific to RHAU isoform 1; this binding is independent of G4 structure. BC200 can act as an acceptor of unwound G4 substrates via a cytosine-rich region and interacts with G4-containing telomerase RNA, suggesting RHAU may direct BC200 to G4-containing targets. RNA co-immunoprecipitation, RNase footprinting, RHAU truncation binding assays, pulldown of endogenous RNAs The Journal of biological chemistry Medium 26740632
2020 The DHX36-specific motif (DSM), OB-fold, and a conserved β-hairpin (β-HP) each contribute to RNA binding and are essential for remodeling of RNA quadruplex and duplex structures. The DSM functions not only as a G4-binding adaptor but also promotes RNA duplex unwinding. Crystal structure of mouse DHX36 bound to ADP reveals conformational changes accompanying ATPase cycle stages. X-ray crystallography (mouse DHX36-ADP), domain deletion/mutagenesis, RNA binding assays, in vitro helicase assays Journal of molecular biology High 32087197
2020 The DHX36-specific motif (DSM) promotes G4 recognition by increasing the G4 binding rate (on-rate) of DHX36 without affecting the dissociation rate. For most G4 substrates, the DSM has little effect on the G4 disruption step, suggesting initial G4 capture and disruption are mechanistically separable. Kinetic binding assays with DHX36 DSM truncation, stopped-flow or competition assays Biological chemistry Medium 33857359
2020 The lncRNA GSEC binds DHX36 via its G4-forming sequence and inhibits DHX36 G-quadruplex unwinding activity. DHX36 knockdown restores reduced migratory activity caused by GSEC knockdown in colon cancer cells, placing DHX36 downstream of GSEC in regulating cell migration. RNA pull-down, G4-unwinding assay with GSEC, siRNA knockdown, cell migration assay Oncogene Medium 27797375
2021 DHX36 is essential for muscle satellite cell (SC) expansion and muscle regeneration. Inducible deletion of Dhx36 in adult SCs causes defective proliferation and muscle regeneration. DHX36 promotes mRNA translation via 5'UTR rG4 binding; specifically, it regulates translation of Gnai2 mRNA by unwinding its 5'UTR rG4, with GNAI2 identified as a downstream effector for SC expansion. Inducible SC-specific conditional knockout mouse, muscle injury model, PAR-CLIP (system-wide DHX36 binding), polysome profiling, in vitro rG4 unwinding assay Nature communications High 34413292
2021 DHX36 depletion suppresses C9orf72 G4C2 repeat-associated non-AUG (RAN) translation in a repeat length-dependent manner, while DHX36 overexpression enhances RAN translation. Upregulation of RAN translation by integrated stress response activation is prevented by DHX36 loss, demonstrating DHX36 promotes translation of G4-forming repeat RNAs. Luciferase reporter assays (cell-based and cell-free), DHX36 depletion and overexpression, integrated stress response induction The Journal of biological chemistry Medium 34174288
2021 RHAU ablation in postnatal cardiomyocytes reduces protein levels of Yap1 and Hexim1 while enhancing their mRNA levels. RHAU associates with both 5' and 3' UTRs of these genes to simultaneously promote translation (via 5'UTR) and destabilize mRNA (via 3'UTR). RHAU-deficient mice develop progressive dilated cardiomyopathy and impaired neonatal heart regeneration. Cardiomyocyte-specific conditional knockout mouse, RNA co-IP (5' and 3'UTR), Western blot, mRNA stability assays The Journal of biological chemistry Medium 33199370
2021 DHX36 deficiency leads to accumulation of DNA damage and slower cell growth; expression of G4-binding-deficient DHX36 mutants only partially rescues these defects. Nuclear DHX36 co-localizes with G4-DNA, RNA polymerase II, and a splicing factor, supporting a role in clearing transcription-associated G4-DNA to maintain genomic integrity. DHX36 depletion, G4-stabilizing drug treatment, DNA damage markers (γH2AX), immunofluorescence co-localization, G4-binding mutant rescue assay Genes to cells Medium 37632696
2022 DHX36 interacts with a rG4 structure in the 5'UTR of ADAR1 mRNA in vitro and in cells. This rG4 normally inhibits ADAR1 translation; DHX36 binding relieves this inhibition in an rG4-dependent manner, as shown in knockdown and knockout conditions. In vitro rG4 characterization, GTFH probes for cellular rG4 detection, DHX36 knockdown/knockout, reporter and native gene translation assays Angewandte Chemie Medium 36300875
2022 The lncRNA Lockd directly interacts with DHX36 (strongest binding at Lockd 5' end) and stabilizes DHX36 interaction with EIF3B; this tripartite complex unwinds the rG4 at Anp32e mRNA 5'UTR to promote ANP32E translation, which is required for myoblast proliferation and muscle regeneration. RNA immunoprecipitation, co-IP, in vitro rG4 unwinding assay, Lockd deletion in vivo, ANP32E translation assays Cell reports Medium 35675771
2023 Dhx36 deletion in differentiated spermatogonia (Stra8-GFPCre) leads to meiotic defects and abnormal spermiogenesis due to dysregulated transcription of G4-harboring genes required for meiosis. Stage-specific conditional knockout mouse, phenotypic analysis of meiosis/spermiogenesis, transcriptome analysis Journal of molecular cell biology Medium 36484653
2024 DHX36 binding induces structural remodeling of mRNA not only at localized binding sites but across entire transcripts, most prominently increasing 3'UTR accessibility. Increased 3'UTR accessibility correlates with decreased mRNA abundance. DHX36 binding sites are enriched for m6A modification and YTHDF1 binding; DHX36-induced structural changes facilitate YTHDF1 binding to m6A sites, leading to mRNA degradation. RNA structurome-seq upon DHX36 depletion, m6A mapping, YTHDF1 CLIP, DHX36 KO cell lines, mRNA abundance assays Nature communications High 39543097
2024 Dhx36 deletion in embryonic or neonatal heart causes dilated cardiomyopathy and failure to develop a ventricular conduction system (VCS). DHX36 deficiency disrupts resolution of promoter G-quadruplexes in key cardiac genes, impacting cardiomyocyte differentiation and Purkinje fiber network morphogenesis. Cardiac conditional knockout mouse, single-nucleus RNA-seq, single-nucleus ATAC-seq, G4 promoter analysis Nature communications High 39366945
2025 Cryo-EM structures of bovine DHX36 bound to a three-tier RNA G4 and a six-tier DNA G4 at 2.6 Å and 3.4 Å resolution respectively reveal that the RecA2 domain of the helicase core plays a key role in DNA vs. RNA discrimination. A sequence-divergent RecA2 surface loop synergizes with the DHX36-specific N-terminal extension to recognize G4 structures over other nucleic acids. Cryo-electron microscopy structure determination, smFRET, site-directed mutagenesis of RecA2 and N-terminal extension Cell reports High 40833853
2025 DHX36 limits stress granule formation; in G3BP1/2 double-knockout cells that strongly inhibit SG formation, reducing DHX36 expression rescues SG-like foci formation, indicating DHX36 can restrain intermolecular RNA-RNA interactions (potentially trans-rG4s) that promote SG assembly. mRNA accumulation in SGs is independent of rG4-forming potential in normal cells. DHX36 depletion in G3BP1/2 KO cells, reporter mRNAs with/without G-tracts, endogenous mRNA SG partitioning by FISH Nucleic acids research Medium 40985767
2025 REV1 C-terminal domain directly interacts with DHX36, requiring a newly defined REV1-interacting region at the DHX36 C-terminus. This interaction coordinates G4 resolution (DHX36 helicase) with suppression of ssDNA gaps during replication of G4-containing DNA. Prolonged G4 stabilization uncouples REV1 and DHX36. Co-immunoprecipitation (direct interaction), domain mapping, REV1 KO cells, G4-stabilizing drug (pyridostatin) treatment, DNA damage assays Nucleic acids research Medium 42258547
2025 DHX36 functions as a rheostat restraining innate immune activation under homeostasis. Exposure to dsRNA reduces DHX36 activity to enable immune activation. DHX36-deficient cells accumulate rG4 structures, show constitutive PKR-dependent stress granule formation, elevated ISG expression, and enhanced RIG-I responsiveness, positioning DHX36 as a regulator linking RNA structure surveillance to PKR- and RIG-I-dependent antiviral signaling. DHX36 KO cells, dsRNA treatment, PKR activation assays, SG formation assays, ISG expression profiling, RIG-I reporter assays, yellow fever virus replicon assay Science advances High 42213826
2025 PCV3 capsid protein interacts with DHX36 via Cap-NLS and DHX36 N-terminal domain (NTD), and promotes K48-linked ubiquitination-dependent degradation of DHX36, thereby antagonizing DHX36-mediated IFN-β production and facilitating PCV3 replication. Co-immunoprecipitation, domain mapping, ubiquitination assay, siRNA knockdown, overexpression, viral replication assay Virology Medium 39862752
2025 RHAU binds the G4 structure in the 3'UTR of StAR (steroidogenic acute regulatory protein) mRNA; conditional RHAU knockdown reduces STAR translation and testosterone levels in mice. RHAU regulates StAR mRNA stability and translation efficiency through this G4 interaction. Circular dichroism, RNA-protein interaction assay, RHAU conditional knockdown mouse, ELISA for testosterone, gene expression analysis Archives of biochemistry and biophysics Medium 41354365
2025 DHX36 directly binds pre-rRNA through its RSM (RHAU-specific motif) in mouse oocytes. DHX36 deletion in oocytes causes G4 accumulation at rDNA and pre-rRNA, insufficient pre-rRNA processing, reduced translation, aberrant chromatin configuration, and complete female infertility. DHX36 overexpression partially rescues pre-rRNA accumulation in knockout oocytes. Oocyte-specific conditional KO mouse, G4 probe/antibody staining, rRNA transcription assay, translation assay, DHX36 overexpression rescue Science bulletin High 40023726
2025 The lncRNA LENT interacts with DHX36 and both associate with ribosomes in 80S and light polysome fractions. LENT modulates DHX36 association with specific mRNAs encoding ER/mitochondrial homeostasis and autophagy regulators, fine-tuning their translation. LENT silencing leads to autophagy, mitophagy, and apoptosis in melanoma cells. RNA immunoprecipitation, polysome fractionation, LENT silencing, ribosome association assay bioRxivpreprint Low

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 306 21703541
2018 Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. Nature 267 29899445
2005 The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates. The Journal of biological chemistry 170 16150737
2004 Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Molecular cell 158 14731398
2015 Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex. Proceedings of the National Academy of Sciences of the United States of America 141 26195789
2019 DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions. Nature communications 137 31160600
2012 The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary. Nucleic acids research 134 22238380
2014 DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation. PLoS pathogens 130 24651521
2018 RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs. Genome biology 128 30591072
2010 Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU. Nucleic acids research 119 20472641
2013 The DEAH-box helicase DHX36 mediates dendritic localization of the neuronal precursor-microRNA-134. Genes & development 103 23651854
2008 Recruitment of the RNA helicase RHAU to stress granules via a unique RNA-binding domain. The Journal of biological chemistry 98 18854321
2011 The DEAH-box RNA helicase RHAU binds an intramolecular RNA G-quadruplex in TERC and associates with telomerase holoenzyme. Nucleic acids research 95 21846770
2016 The novel G-quadruplex-containing long non-coding RNA GSEC antagonizes DHX36 and modulates colon cancer cell migration. Oncogene 90 27797375
2010 The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation. Molecular and cellular biology 89 21149580
2019 RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36. Nature communications 70 31015431
2013 The RNA helicase RHAU (DHX36) suppresses expression of the transcription factor PITX1. Nucleic acids research 70 24369427
2015 Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development. Cell reports 65 26489465
2021 Translational control by DHX36 binding to 5'UTR G-quadruplex is essential for muscle stem-cell regenerative functions. Nature communications 63 34413292
2013 Binding of G-quadruplexes to the N-terminal recognition domain of the RNA helicase associated with AU-rich element (RHAU). The Journal of biological chemistry 50 24151078
2012 The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis. Blood 49 22422825
2016 RHAU helicase stabilizes G4 in its nucleotide-free state and destabilizes G4 upon ATP hydrolysis. Nucleic acids research 46 28069994
2011 Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 46 21590736
2016 The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3'-End Processing Following UV-Induced DNA Damage. Journal of molecular biology 44 27940037
2008 Transcription-dependent nucleolar cap localization and possible nuclear function of DExH RNA helicase RHAU. Experimental cell research 43 18279852
2016 RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3'-Tail of the Long Non-coding RNA BC200 (BCYRN1). The Journal of biological chemistry 42 26740632
2018 Molecular Mechanistic Insights into Drosophila DHX36-Mediated G-Quadruplex Unfolding: A Structure-Based Model. Structure (London, England : 1993) 41 29429875
2021 The RNA helicase DHX36-G4R1 modulates C9orf72 GGGGCC hexanucleotide repeat-associated translation. The Journal of biological chemistry 38 34174288
2017 The G-quadruplex (G4) resolvase DHX36 efficiently and specifically disrupts DNA G4s via a translocation-based helicase mechanism. The Journal of biological chemistry 35 29269411
2015 A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation. Cell death & disease 35 25611385
2021 G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging. Aging 30 34862880
2020 SMaRT lncRNA controls translation of a G-quadruplex-containing mRNA antagonizing the DHX36 helicase. EMBO reports 25 32337838
2022 An RNA G-Quadruplex Structure within the ADAR 5'UTR Interacts with DHX36 Helicase to Regulate Translation. Angewandte Chemie (International ed. in English) 24 36300875
2017 G-quadruplexes unfolding by RHAU helicase. Biochimica et biophysica acta. General subjects 24 28065761
2022 Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation. Cell reports 20 35675771
2007 RhaU of Rhizobium leguminosarum is a rhamnose mutarotase. Journal of bacteriology 20 18156270
2015 Biochemical characterization of G4 quadruplex telomerase RNA unwinding by the RNA helicase RHAU. Methods in molecular biology (Clifton, N.J.) 19 25579584
2015 Biophysical Characterization of G-Quadruplex Recognition in the PITX1 mRNA by the Specificity Domain of the Helicase RHAU. PloS one 19 26649896
2019 Recognition of different base tetrads by RHAU (DHX36): X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex. Journal of structural biology 18 31586599
2020 Function of Auxiliary Domains of the DEAH/RHA Helicase DHX36 in RNA Remodeling. Journal of molecular biology 16 32087197
2019 Molecular characterization and expression of the teleost cytosolic DNA sensor genes cGAS, LSm14A, DHX9, and DHX36 in Japanese medaka, Oryzias latipes. Developmental and comparative immunology 15 31141705
2023 piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2. Non-coding RNA research 14 36710986
2021 Mechanism of recognition of parallel G-quadruplexes by DEAH/RHAU helicase DHX36 explored by molecular dynamics simulations. Computational and structural biotechnology journal 13 34025941
2002 Molecular cloning and characterization of human DDX36 and mouse Ddx36 genes, new members of the DEAD/H box superfamily. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 13 12198572
2024 DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1. Nature communications 12 39543097
2020 The G4 resolvase RHAU modulates mRNA translation and stability to sustain postnatal heart function and regeneration. The Journal of biological chemistry 12 33199370
2023 DHX36 maintains genomic integrity by unwinding G-quadruplexes. Genes to cells : devoted to molecular & cellular mechanisms 11 37632696
2023 DNA/RNA helicase DHX36 is required for late stages of spermatogenesis. Journal of molecular cell biology 10 36484653
2020 The DHX36-specific-motif (DSM) enhances specificity by accelerating recruitment of DNA G-quadruplex structures. Biological chemistry 10 33857359
2018 RNAi-mediated knockdown of the Rhau helicase preferentially depletes proteins with a Guanine-quadruplex motif in the 5'-UTR of their mRNA. Biochemical and biophysical research communications 10 30528389
2020 Identification of DHX36 as a tumour suppressor through modulating the activities of the stress-associated proteins and cyclin-dependent kinases in breast cancer. American journal of cancer research 9 33414996
2022 RHAU Peptides Specific for Parallel G-Quadruplexes: Potential Applications in Chemical Biology. Molecular biotechnology 8 35984625
2025 RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells. Nucleic acids research 7 39883012
2024 Exploring the biological roles of DHX36, a DNA/RNA G-quadruplex helicase, highlights functions in male infertility: A comprehensive review. International journal of biological macromolecules 7 38677694
2024 The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development. Nature communications 7 39366945
2021 Using Magnetic Tweezers to Unravel the Mechanism of the G-quadruplex Binding and Unwinding Activities of DHX36 Helicase. Methods in molecular biology (Clifton, N.J.) 7 33201470
2021 The G4 resolvase RHAU regulates ventricular trabeculation and compaction through transcriptional and post-transcriptional mechanisms. The Journal of biological chemistry 7 34838591
2025 DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice. Science bulletin 6 40023726
2022 To unwind the biological knots: The DNA/RNA G-quadruplex resolvase RHAU (DHX36) in development and disease. Animal models and experimental medicine 6 35789129
2025 Structural basis for dual DNA and RNA specificity of the G-quadruplex-resolving DEAH-box helicase DHX36. Cell reports 4 40833853
2020 DHX36, BAX, and ARPC1B May Be Critical for the Diagnosis and Treatment of Tuberculosis. Canadian respiratory journal 4 32774561
2020 Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers. Head & neck 4 33006201
2024 Specific binding of G-quadruplex in SARS-CoV-2 RNA by RHAU peptide. Current research in structural biology 3 38292819
2020 G-Quadruplex Helicase DHX36/G4R1 Engages Nuclear Lamina Proteins in Quiescent Breast Cancer Cells. ACS omega 3 33015511
2020 Competition of Ligands and the 18-mer Binding Domain of the RHAU Helicase for G-Quadruplexes: Orthosteric or Allosteric Binding Mechanism? Chemistry (Weinheim an der Bergstrasse, Germany) 3 33617136
2003 Expression research for human DDX36 and mouse Ddx36 gene in the adult testis. Yi chuan xue bao = Acta genetica Sinica 3 12812084
2025 DHX36 modulates stress granule assembly independent of recruitment of mRNAs with G-quadruplex sequence motifs. Nucleic acids research 2 40985767
2023 Letter to editor regarding "piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2". Non-coding RNA research 2 37662498
2019 Correction to: RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs. Genome biology 2 31215477
2025 Ubiquitination-dependent degradation of DHX36 mediated by porcine circovirus type 3 capsid protein. Virology 1 39862752
2025 DHX36 plays an oncogenic role in breast cancer progression and invasiveness. Scientific reports 1 41331054
2025 RHAU helicase affects testosterone synthesis by regulating the Star 3' UTR region. Archives of biochemistry and biophysics 1 41354365
2026 Molecular dynamics simulations elucidate the structural determinants of size-exclusion chromatography behavior in dimeric G-quadruplex-RHAU. Journal of chromatography. A 0 41544432
2026 From alkylating to shape-shifting G-quadruplex ligands: the RHAU peptide story. Nucleic acids research 0 41607284
2026 Extreme Kinetic Stability and RNase Resistance of Human Telomerase RNA G-Quadruplexes Overcome by DHX36 Helicase. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41691481
2026 DHX36 is a regulatory switch in the interferon-mediated antiviral response. Science advances 0 42213826
2026 Human REV1 interacts with DHX36 to promote replication and tolerance of G-quadruplex DNA. Nucleic acids research 0 42258547
2025 Corrigendum to "piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2" [Noncoding RNA Research 2023 8 (2) 174-186]. Non-coding RNA research 0 40124961
2025 Host helicase DHX36 inhibits pseudorabies virus proliferation by unwinding the G-quadruplex in the 3'UTR of IE180. Veterinary microbiology 0 40349494
2025 Opposite Effects of Added AsPh3 Reveal a Drastic Mechanistic Switch in RhI/AuI Transmetalations via Rh-Au Bonded Intermediates. Inorganic chemistry 0 40571906
2025 Impact of G-tract RNAs and the DHX36 helicase on stress granule composition and formation. bioRxiv : the preprint server for biology 0 40667105
2025 Dhx36 deficiency accelerates BMSC senescence and promotes age-related bone loss. BMB reports 0 41276281
2019 Correction to: RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs. Genome biology 0 30635026

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