RNA Helicase Function in Cancer Biology

RNA helicases are enzymes that harness the energy of nucleotide hydrolysis to remodel RNA structures and ribonucleoprotein complexes. In cancer biology, members of the DExD/H-box family regulate critical processes including transcription, splicing, translation initiation, RNA decay and ribosome biogenesis. Dysregulated helicase activity can perturb genome stability, alter alternative splicing patterns, modulate stress responses and influence oncogenic signalling. Certain helicases act as tumour promoters by enhancing proliferation, metastasis and treatment resistance, whereas others facilitate DNA damage recognition and apoptosis, exhibiting oncosuppressive functions. The dual roles of these enzymes reflect context-dependent interactions with specific RNA substrates and protein partners, highlighting their potential as biomarkers and targets for precision oncology. Advances in structural biology and biophysical methods have begun to unravel the mechanisms of RNA binding and duplex unwinding, informing the design of small-molecule inhibitors and molecular degraders that selectively impair tumour-promoting activities while sparing normal tissues.

Research from Nature Portfolio

Recent studies have provided atomistic and thermodynamic insights into the unwinding mechanism of a prototypical DEAD-box helicase. High-resolution nuclear magnetic resonance analyses have demonstrated that the helicase preferentially binds single-stranded RNA, stabilising a domain-closed conformation that underpins efficient duplex destabilisation. These findings elucidate how differential binding affinities guide substrate recognition and remodelling across diverse RNA targets. Complementary structural work has captured a pre-unwound complex with a short double-stranded RNA, revealing that two helicase cores cooperate to engage distinct strands and that ATP-induced conformational changes drive stepwise separation of base pairs. Together, these advances delineate a cohesive model for ATP-dependent RNA remodelling, with implications for therapeutic modulation of helicase-mediated pathways in malignancy.

RNA Helicase Function in Cancer Biology publication trend

The graph below shows the total number of articles in rna helicase function in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

DEAD-box helicase: A subfamily of RNA helicases characterised by the conserved Asp-Glu-Ala-Asp motif, which catalyses ATP-dependent RNA duplex unwinding.

Alternative splicing: A post-transcriptional process by which different combinations of exons are joined to generate multiple mRNA isoforms from a single gene.

Autophagy: A lysosomal degradation pathway that recycles cellular components, often co-opted by cancer cells to survive metabolic stress.

Stress granule: A cytoplasmic assembly of stalled translation pre-initiation complexes formed in response to cellular stress, modulated by specific helicases.

Duplex RNA: A double-stranded region within an RNA molecule, which can form secondary structures requiring helicase activity to resolve.

References

1. NMR characterization of RNA binding property of the DEAD-box RNA helicase DDX3X and its implications for helicase activity. Nature Communications (2024).
2. Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy. Theranostics (2025).
3. Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence. Journal of Experimental & Clinical Cancer Research (2023).
4. AEP-cleaved DDX3X induces alternative RNA splicing events to mediate cancer cell adaptation in harsh microenvironments. Journal of Clinical Investigation (2023).
5. The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X. Nature Communications (2019).