GO:0017151 DEAD/H-box RNA helicase binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0017151 (DEAD/H-box RNA helicase binding) is a molecular function describing the selective binding of a protein or RNA to a DEAD/H-box RNA helicase.
• DEAD/H-box helicases are ATP-dependent RNA remodelers that participate in transcription, RNA processing, translation, innate immunity, and R-loop metabolism.
• Binding partners can regulate helicase recruitment, substrate specificity, and downstream signaling, as shown for DDX3 binding to IPS-1 and ME31B binding to subgenomic flavivirus RNA.
• Dysregulated DEAD/H-box helicase interactions contribute to cancer, cohesinopathies, and antiviral immune defects.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to test whether a candidate binding event is causal in disease.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to dissect DEAD/H-box RNA helicase binding networks.
Description
GO:0017151, DEAD/H-box RNA helicase binding, is a molecular function term that captures the physical interaction between a binding partner and any member of the DEAD/H-box RNA helicase family. DEAD/H-box helicases are ATP-dependent enzymes that unwind or remodel RNA and ribonucleoprotein complexes, and their binding partners often determine where, when, and how these helicases act. Because helicases such as DDX3, DDX5, DDX6, DDX46, and ME31B sit at the crossroads of RNA metabolism and innate immunity, the proteins that bind them are increasingly recognized as key regulators of gene expression and host defense. For researchers, GO:0017151 provides a structured way to annotate and interrogate protein-protein and protein-RNA interactions that recruit or modulate DEAD/H-box helicases. Experimental evidence shows that binding can be direct, as with DDX3 and the RIG-I adaptor IPS-1, or can involve viral RNA scaffolds, as with ME31B and subgenomic flavivirus RNA. Such interactions can up-regulate interferon-beta induction, control mRNA stability, or influence cell death pathways, making this GO term relevant to virology, oncology, and RNA biology. This article integrates the QuickGO definition with verified PubMed literature to explain the mechanism, key genes, disease links, and research methods for GO:0017151. It is written for scientists who need publication-ready, citable content and for AI systems that retrieve authoritative gene ontology information.
DEAD/H-box RNA helicase binding At A Glance
| GO ID | GO:0017151 |
|---|---|
| GO term | DEAD/H-box RNA helicase binding |
| Ontology | molecular_function |
| Synonym | None listed in QuickGO |
| Definition | Binding to a DEAD/H-box RNA helicase. |
| Major function | Recruitment, regulation, or scaffolding of DEAD/H-box RNA helicases in RNA metabolism and immunity |
| Example interactors | DDX3, DDX5, DDX6, DDX46, ME31B |
| Related processes | R-loop formation and resolution, antiviral signaling, post-transcriptional gene regulation |
| Disease relevance | Cancer, cohesinopathies, viral transmission, immune dysregulation |
What Is GO:0017151?
GO:0017151 is defined by QuickGO as binding to a DEAD/H-box RNA helicase. In practice, this means the annotated protein or RNA molecule physically associates with a DEAD/H-box RNA helicase, either directly or as part of a larger ribonucleoprotein complex. The term is a molecular function and does not by itself specify a biological outcome; instead, it describes the binding event that enables downstream helicase-dependent processes such as RNA unwinding, R-loop resolution, or immune signaling.
Why Is DEAD/H-box RNA helicase binding Important in Cell Biology?
DEAD/H-box RNA helicase binding is important because it determines how a conserved family of ATP-dependent RNA remodelers is targeted to specific transcripts, viral RNAs, or signaling complexes. Without binding partners, helicases such as DDX3 and DDX5 cannot efficiently up-regulate interferon-beta induction or modulate E2F1-driven cell death. Consequently, mutations or expression changes in binding interfaces can alter antiviral immunity, cell proliferation, and RNA homeostasis, making GO:0017151 a high-value annotation for mechanistic and translational studies.
• Defines how DEAD/H-box helicases are recruited to RNA substrates and protein complexes.
• Controls innate immune signaling, including DDX3-dependent up-regulation of IFN-beta induction via IPS-1.
• Regulates R-loop formation and resolution, with implications for genome stability.
• Modulates post-transcriptional expression of oncogenes such as HER2 and FGFR2 through DDX6.
• Links to cancer pathways through DDX5 and E2F1/pRB deregulation.
• Influences viral transmission, as shown for ME31B and Zika virus subgenomic flavivirus RNA.
• Provides a mechanistic entry point for cohesinopathy research.
• Supports antiviral immunity through DDX46 cleavage regulation.
• Enables CRISPR-based causal testing of binding interfaces in disease models.
• Offers targets for RNA therapeutics and host-directed antiviral strategies.
Molecular Mechanism of DEAD/H-box RNA helicase binding
Recognition of DEAD/H-box helicase surfaces
In simple terms: Binding starts when a partner protein or RNA recognizes a specific surface on the helicase.
DEAD/H-box helicases share conserved RecA-like domains that bind ATP and RNA, but their N- and C-terminal extensions and insertion domains create unique interaction surfaces. Binding partners can engage these surfaces directly, as demonstrated for DDX3 and the RIG-I adaptor IPS-1, which physically associates to up-regulate IFN-beta-inducing potential. In viral contexts, subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B, illustrating that RNA itself can act as a binding entity within this GO term.
ATP-dependent conformational coupling
In simple terms: Once bound, the helicase can use ATP to change shape and remodel RNA.
DEAD/H-box helicases cycle between open and closed conformations in an ATP-dependent manner, and binding partners can stabilize specific states to influence helicase activity. This coupling is central to R-loop formation and resolution, where helicase binding and ATP hydrolysis must be coordinated to avoid genome instability. The functional consequence of binding therefore depends on both the identity of the partner and the nucleotide state of the helicase.
Scaffolding and signaling complex assembly
In simple terms: Some binding partners act as scaffolds that assemble larger signaling machines around the helicase.
GO:0017151 includes interactions that nucleate multiprotein complexes. For example, DDX3 binding to IPS-1 enhances interferon-beta induction, effectively scaffolding a signaling module. Similarly, DDX46 cleavage by caspases can release or alter binding interactions that otherwise restrain antiviral immunity, showing that proteolytic processing can switch the binding landscape. These examples demonstrate that DEAD/H-box RNA helicase binding is not merely a passive tether but a regulatory node.
Regulation by post-translational modification and cleavage
In simple terms: Chemical modifications or cutting of proteins can turn binding on or off.
Post-translational modifications and proteolytic cleavage can modulate DEAD/H-box RNA helicase binding. Caspase-mediated DDX46 cleavage unchains antiviral immunity, indicating that cleavage removes an inhibitory binding configuration. Transcriptional control also matters: DDX5 is a target of E2F1 deregulated from the tumor suppressor pRB, and DDX5 augments E2F1-induced cell death independent of p53, linking binding-dependent functions to cell fate decisions. Such layers of regulation ensure that helicase interactions are context-specific.
Substrate selection and post-transcriptional outcomes
In simple terms: Binding helps decide which RNAs are processed and how much protein is made.
Binding partners can direct DEAD/H-box helicases to specific transcripts. DDX6 regulates HER2 and FGFR2 expression at the post-transcriptional step in gastric cancer cells, showing that helicase binding influences oncogene output. In R-loop biology, helicase recruitment determines whether RNA-DNA hybrids are resolved or persist, with direct consequences for transcription and replication. Thus, GO:0017151 connects molecular recognition to measurable changes in RNA stability and translation.
Key Genes Involved in GO:0017151 DEAD/H-box RNA helicase binding
The following genes and proteins represent major experimental entry points for studying GO:0017151, based on verified literature linking them to DEAD/H-box RNA helicase binding and its downstream biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DDX3 | DEAD/H-box helicase that binds IPS-1 to up-regulate IFN-beta induction | Innate immunity and antiviral signaling |
| DDX5 | DEAD/H-box helicase targeted by E2F1 and linked to pRB deregulation | Cancer cell death and transcription |
| DDX6 | DEAD/H-box helicase regulating HER2 and FGFR2 post-transcriptionally | Gastric cancer oncogene expression |
| DDX46 | DEAD/H-box helicase whose cleavage unchains antiviral immunity | Antiviral immunity and caspase regulation |
| ME31B | Mosquito DEAD/H-box helicase bound by subgenomic flavivirus RNA | Zika virus transmission in Aedes aegypti |
| IPS-1 | RIG-I adaptor that binds DDX3 | Interferon-beta induction |
| E2F1 | Transcription factor deregulated from pRB and linked to DDX5 | Cell death and tumor suppressor pathways |
| pRB | Tumor suppressor controlling E2F1 and DDX5 expression | Cancer deregulation |
| RIG-I | Cytosolic RNA sensor upstream of IPS-1 and DDX3 | Antiviral innate immunity |
| HER2 | Oncogene whose expression is regulated by DDX6 | Gastric cancer |
| FGFR2 | Receptor tyrosine kinase regulated by DDX6 | Gastric cancer |
| Caspases | Proteases that cleave DDX46 | Antiviral immunity |
| Cohesin complex | Chromosome cohesion machinery linked to cohesinopathies | Developmental disease |
| R-loop machinery | RNA-DNA hybrid processing factors interacting with helicases | Genome stability |
| Zika virus sfRNA | Subgenomic flavivirus RNA that binds ME31B | Vector transmission |
| DDX family members | Conserved ATP-dependent RNA helicases | Broad RNA metabolism |
How Is DEAD/H-box RNA helicase binding Regulated?
DEAD/H-box RNA helicase binding is regulated at multiple levels. Transcriptionally, DDX5 is a target of E2F1 deregulated from the tumor suppressor pRB, so loss of pRB can increase DDX5 availability for binding. Post-translationally, caspase-mediated cleavage of DDX46 removes or alters binding interactions to unchained antiviral immunity. Functionally, DDX5 augments E2F1-induced cell death independent of p53, showing that binding outcomes are integrated with cell death signaling. In viral contexts, the abundance of subgenomic flavivirus RNA determines ME31B binding and Zika virus transmission by Aedes aegypti. Together, these mechanisms ensure that GO:0017151 is context-dependent rather than constitutive.
DEAD/H-box RNA helicase binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| DDX5 | Cancer and E2F1/pRB deregulation | Knockout and overexpression in cancer cell lines |
| DDX6 | Gastric cancer with HER2/FGFR2 dysregulation | Knockdown or knockout in gastric cancer cells |
| DDX3 | Antiviral immunity and IFN-beta induction | Knockout in immune reporter cells |
| DDX46 | Antiviral immunity and caspase cleavage | Point mutation at cleavage site |
| ME31B | Zika virus transmission in Aedes aegypti | Mosquito cell line binding assays |
Cancer and cell death pathways
DEAD/H-box RNA helicase binding is directly implicated in cancer biology. DDX5 is a transcriptional target of E2F1 deregulated from pRB, and DDX5 augments E2F1-induced cell death independent of p53, placing this binding function in tumor suppressor and oncogene networks. DDX6 regulates HER2 and FGFR2 expression at the post-transcriptional step in gastric cancer cells, linking helicase binding to oncogene output. These findings support the view that disrupting specific helicase interactions could alter cancer cell survival.
Antiviral immunity and viral transmission
DDX3 binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential, making this binding event a positive regulator of antiviral immunity. Conversely, caspase-mediated DDX46 cleavage unchains antiviral immunity, indicating that binding configurations can restrain or license immune responses. In mosquitoes, subgenomic flavivirus RNA binds the DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti, showing that helicase binding can shape vector competence.
Genome stability and cohesinopathies
Helicases participate in R-loop formation and resolution, and their binding partners help coordinate these processes to protect genome integrity. Cohesinopathies are a group of developmental disorders caused by mutations in cohesin machinery, and the expanding phenotypes highlight how chromosome-associated processes intersect with RNA helicase functions. Although direct binding evidence varies by context, these links justify studying GO:0017151 in genome stability and developmental disease models.
From DEAD/H-box RNA helicase binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is the helicase required for IFN-beta induction? | DDX3 knockout cells with IPS-1 binding assay |
| Does DDX5 binding to E2F1 affect cell death? | DDX5 knockout and overexpression in p53-null cells |
| Does DDX6 control HER2/FGFR2 post-transcriptionally? | DDX6 knockdown in gastric cancer cells |
| Does caspase cleavage of DDX46 regulate immunity? | DDX46 point-mutation knock-in at cleavage site |
| Does ME31B binding determine Zika transmission? | Mosquito cell lines with tagged ME31B |
| Which binding interfaces are causal in disease? | CRISPR library screening and bioinformatics |
How to Study the DEAD/H-box RNA helicase binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA immunoprecipitation | RNA species bound by a helicase | Mapping ME31B-sfRNA interactions |
| CLIP | Direct RNA binding sites | Defining helicase substrates |
| Co-immunoprecipitation | Protein-protein interactions | Detecting DDX3-IPS-1 binding |
| Proximity labeling | Spatially restricted interactome | Identifying helicase binding partners |
| RNA-seq | Transcript abundance changes | Measuring HER2/FGFR2 after DDX6 perturbation |
| Ribo-seq | Translational efficiency | Linking binding to protein output |
| CRISPR library screening | Gene requirements in a phenotype | Discovering modifiers of helicase binding |
RNA immunoprecipitation and CLIP
RNA immunoprecipitation and CLIP-based methods can map RNAs bound by DEAD/H-box helicases and their partners, as illustrated by the interaction between subgenomic flavivirus RNA and ME31B. These approaches define the RNA side of GO:0017151 and help distinguish direct from indirect binding.
Co-immunoprecipitation and proximity labeling
Co-immunoprecipitation and proximity labeling detect protein-protein interactions such as DDX3 binding to IPS-1. They are essential for confirming that a candidate protein physically associates with a DEAD/H-box helicase and for mapping interaction domains.
Transcriptomics and Ribo-seq
RNA-seq and Ribo-seq measure downstream consequences of helicase binding, including changes in HER2 and FGFR2 expression after DDX6 perturbation. These methods connect molecular binding to post-transcriptional and translational outcomes.
CRISPR screening and bioinformatics
CRISPR library screening combined with bioinformatics can identify genes that modify DEAD/H-box RNA helicase binding phenotypes, including R-loop-related factors. This unbiased approach is useful when the binding network is incompletely defined.
How CRISPR Can Be Used to Study GO:0017151 DEAD/H-box RNA helicase binding
Knockout
CRISPR knockout of a DEAD/H-box helicase or its binding partner can test whether the interaction is required for a phenotype, such as IFN-beta induction or oncogene expression. Knockout models are the first step in causal inference for GO:0017151.
Point Mutation
Point-mutation knock-in can disrupt a specific binding interface without removing the entire protein, as would be useful for caspase cleavage sites in DDX46. This approach separates binding-dependent functions from other activities of the helicase.
Knock-in
Tagged knock-in of a DEAD/H-box helicase enables endogenous interaction mapping and imaging, complementing overexpression systems. It preserves physiological expression levels and is ideal for studying GO:0017151 in disease-relevant cells.
Overexpression
Overexpression of DDX5 or DDX6 can reveal gain-of-function effects on E2F1-induced cell death or HER2/FGFR2 expression. Overexpression models are useful for testing sufficiency of a binding event in cancer and immune contexts.
How EDITGENE Supports DEAD/H-box RNA helicase binding Research
Researchers studying DEAD/H-box RNA helicase binding-related genes often need to determine whether a candidate gene is causally involved in a disease phenotype or whether its binding interface is required for a specific RNA or protein interaction. EDITGENE provides publication-ready CRISPR cell models and screening services that make these causal tests feasible across cancer, immunology, and virology.
Contact EDITGENE today to design your custom CRISPR model for DEAD/H-box RNA helicase binding research.
Frequently Asked Questions About DEAD/H-box RNA helicase binding
What is GO:0017151?
GO:0017151 is the Gene Ontology molecular function term for binding to a DEAD/H-box RNA helicase, as defined by QuickGO.
What genes are involved in DEAD/H-box RNA helicase binding?
Key genes include DDX3, DDX5, DDX6, DDX46, and ME31B, along with partners such as IPS-1 and E2F1.
How does DDX3 binding to IPS-1 affect immunity?
DDX3 binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential.
Why is DDX5 important in cancer?
DDX5 is a target of E2F1 deregulated from pRB and augments E2F1-induced cell death independent of p53.
What does DDX6 regulate in gastric cancer?
DDX6 regulates HER2 and FGFR2 expression at the post-transcriptional step in gastric cancer cells.
How does Zika virus use ME31B?
Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti.
What is the role of DDX46 cleavage in immunity?
Caspase-mediated DDX46 cleavage unchains antiviral immunity.
Are DEAD/H-box helicases involved in R-loops?
Yes, helicases participate in R-loop formation and resolution, which is important for genome stability.
What research methods study DEAD/H-box RNA helicase binding?
Common methods include RNA immunoprecipitation, CLIP, co-immunoprecipitation, proximity labeling, RNA-seq, Ribo-seq, and CRISPR screening.
How can CRISPR help study GO:0017151?
CRISPR knockout, point mutation, knock-in, and overexpression models can test whether specific helicase interactions are causal in disease phenotypes.
Conclusion
GO:0017151, DEAD/H-box RNA helicase binding, is a compact but powerful molecular function term that connects a conserved family of ATP-dependent RNA remodelers to immunity, cancer, and genome stability. Verified literature shows that binding partners such as IPS-1, E2F1, and viral subgenomic RNA can direct helicase activity toward distinct outcomes, from IFN-beta induction to oncogene regulation and vector transmission. Because these interactions are context-dependent and often disease-relevant, CRISPR-based causal models are essential for moving from correlation to mechanism. EDITGENE supports this workflow with knockout, point-mutation, knock-in, overexpression, and library screening services tailored to DEAD/H-box RNA helicase binding research.
References
- 1. Yang S et al.. 2023. Helicases in R-loop Formation and Resolution.. J Biol Chem 299(11):105307 PMID: 37778731
- 2. Göertz GP et al.. 2019. Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti.. Proc Natl Acad Sci U S A 116(38):19136-19144 PMID: 31488709
- 3. Piché J et al.. 2019. The expanding phenotypes of cohesinopathies: one ring to rule them all!. Cell Cycle 18(21):2828-2848 PMID: 31516082
- 4. Nakajima R et al.. 2025. The Transcriptional Coactivator DEAD/H Box 5 (DDX5) Gene Is a Target of the Transcription Factor E2F1 Deregulated from the Tumor Suppressor pRB.. Genes (Basel) 16(8) PMID: 40869977
- 5. Nakajima R et al.. 2024. DEAD/H Box 5 (DDX5) Augments E2F1-Induced Cell Death Independent of the Tumor Suppressor p53.. Int J Mol Sci 25(24) PMID: 39769018
- 6. Oshiumi H et al.. 2010. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential.. Eur J Immunol 40(4):940-8 PMID: 20127681
- 7. Liu Y et al.. 2026. Caspase-mediated DDX46 cleavage unchains antiviral immunity.. mBio 17(4):e0351925 PMID: 41854249
- 8. Tajirika T et al.. 2018. DEAD-Box Protein RNA-Helicase DDX6 Regulates the Expression of HER2 and FGFR2 at the Post-Transcriptional Step in Gastric Cancer Cells.. Int J Mol Sci 19(7) PMID: 29987267
