Researchers at Northwestern University and the University of Cambridge have identified how the RNA helicase domain of the enzyme N-acetyltransferase 10 drives tumor growth, according to a peer-reviewed study published in Nature Communications.
The study found that N-acetyltransferase 10, known as NAT10, promotes cancer cell proliferation through its RNA helicase domain rather than its RNA acetyltransferase domain. NAT10 is a multifunctional enzyme recognized as a therapeutic vulnerability in solid and hematological malignancies. To evaluate its function, the research team coupled Proteolysis Targeting Chimera-mediated degradation of NAT10 with a deep mutational scanning assay, followed by testing in biochemical assays, human cell lines, and female mouse xenografts.
The proliferative action of NAT10 operates independently of RNA acetylation but requires RNA-binding activity. The enzyme's RNA helicase domain binds to 18S rRNA and promotes the biogenesis of the 40S ribosomal subunit. At the same time, this domain interferes with the deposition of m¹acp³Ψ, a conserved chemical modification on 18S rRNA. The resulting loss of m¹acp³Ψ generates hypomodified ribosomes that accelerate cancer cell growth and tumor formation.
Mahmood H. Dalhat and Sharath Narayan served as equal co-lead authors on the project, working alongside corresponding authors Daniel Arango and Konstantinos Tzelepis. The work utilized resources from the Flow Cytometry Core Facility at the Robert H. Lurie Comprehensive Cancer Center and the Quest High-Performance Computing Facility at Northwestern University.
The paper noted that author Konstantinos Tzelepis holds stock options, consultancy fees, and research funding from Storm Therapeutics Ltd., and is a stockholder in TEP Therapeutics Inc. The study, accepted on July 27, 2026, and published on August 8, 2026, establishes the RNA helicase domain of NAT10 as a potential target for therapeutic intervention.
