Exeter Scientists Uncover Non-Coding DNA "Hidden" Causes for Neonatal Autoimmune Diabetes

Exeter researchers discover that mutations in non-coding RNA genes RNU4ATAC and RNU6ATAC cause rare neonatal autoimmune diabetes.

By: AXL Media

Published: Apr 9, 2026, 11:08 AM EDT

Source: Information for this report was sourced from the University of Exeter.

Decoding the Non-Coding Genome

For decades, genetic research has focused primarily on "coding" genes—the 2% of the human genome responsible for producing proteins. However, a new study published in the American Journal of Human Genetics has shifted the spotlight to the often-overlooked "non-coding" regions. Researchers found that functional RNA molecules, which regulate how genetic information is read and interpreted, can be the root cause of rare diseases. This discovery highlights a significant territory in the human genome that may hold the answers for the nearly 50% of individuals with rare conditions who currently lack a definitive genetic diagnosis.

The Role of RNU4ATAC and RNU6ATAC

Using advanced genome sequencing, the Exeter team identified bi-allelic variants in two genes: RNU4ATAC and RNU6ATAC. These genes are critical components of the "minor spliceosome," a molecular machine that edits genetic instructions before they are used by the cell. In 19 children from around the world, mutations in these non-coding genes were found to be the cause of neonatal diabetes—a rare form of the condition that appears within the first six months of life. Because these genes do not make proteins, they had been historically skipped over by standard diagnostic tests, leaving families without answers until now.

A Cascade of Immune Disruption

The impact of these mutations is not localized to a single biological pathway. Computational analysis revealed that the disruption in these two RNA genes causes a "domino effect," affecting the expression of approximately 800 other genes. Many of these secondary genes are essential for the regulation of the immune system. This widespread disruption leads to an autoimmune attack on the insulin-producing beta cells in the pancreas, similar to the process seen in more common type 1 diabetes. By mapping this cascade, scientists can now identify exactly which of these 800 genes are the primary drivers of autoimmune destruction.