The findings are reported today in two companion papers published in Nature and Nature Genetics.
The studies, led by scientists including Professor Nicola Whiffin (Department of Paediatrics, Centre for Human Genetics), Dr. Gregory Findlay (Francis Crick Institute) and Professor Cas Simons (Centre for Population Genomics, Australia), focus on RNU4-2, a non-coding gene that produces a small RNA molecule essential for RNA splicing — a fundamental cellular process required to correctly process genetic information.
A non-coding gene with a major impact on disease
Unlike most genes implicated in human disease, RNU4-2 does not encode a protein. Instead, it produces an RNA component of the ‘spliceosome’, the molecular machinery that edits RNA before it is translated into proteins.
Previous work led by Professor Whiffin in 2024, using data in Genomics England’s National Genomic Research Library, identified that specific mutations in RNU4-2 cause ReNU syndrome, a neurodevelopmental disorder. Around 20 mutations in a small critical region of the gene are now known to cause this condition.
The discovery was striking: these mutations are estimated to account for approximately 100,000 cases of neurodevelopmental disorders globally, making ReNU syndrome one of the most prevalent known neurodevelopmental disorders. This was the first time a non-coding gene was found with such a significant role in any rare disorder. To top it all, the RNU4-2 gene is tiny: at only 145 DNA bases long it is 100-times smaller than most known disease causing genes.
Read the full story on the Department of Paediatrics website.