NAT10’s helicase domain fuels tumor growth in lab and animal models

A library of more than 1,900 versions of one enzyme went into a single cellular contest. In Northwestern Medicine’s experiment, each NAT10 variant carried one amino acid substitution; versions that slowed cancer-cell proliferation dropped out as the cells multiplied. The result pointed to one specific region: NAT10’s RNA helicase domain, not the part that chemically modifies RNA.

NAT10 has been linked to several cancers, including hepatocellular carcinoma and acute myeloid leukemia. Its RNA acetyltransferase activity—the function that adds a chemical modification to RNA—had been a disputed explanation for its cancer-promoting behavior. The new experiments instead found that the helicase domain was required for proliferation and tumor growth, while the acetyltransferase activity was not.

The mechanism involves ribosomes, the cell structures that help make proteins. The researchers found that NAT10 binds to ribosomes through its RNA helicase function and reduces deposition of the RNA modification m1acp3Y. That creates a subpopulation of hypomodified, or less chemically modified, ribosomes that supports cancer-cell growth.

The team backed the screening result with biochemical, cellular and animal models. The findings, published in Nature Communications on August 24, 2026, suggest that efforts to target NAT10 may need to focus on its helicase domain rather than its RNA acetyltransferase activity. Daniel Arango, an assistant professor of pharmacology at Northwestern and a co-corresponding author, said the next step is to develop tailored therapeutic strategies through collaboration across disciplines.

And concretely? The study identifies a more precise molecular target and a mechanism relevant to treatment research: NAT10’s RNA helicase domain is a potential target for cancer treatment. The published work reports biochemical, cellular and animal models.