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An international team led by Monash University researchers has uncovered the genetic code governing the way genetic mutations affect mRNA and result in disease.

This breakthrough, detailed in a new paper in Nature Communications, paves the way for mRNA therapeutics that could address serious disease, particularly under-researched conditions that are rare or population-specific. The code allows researchers to look inside RNA splicing, an essential cellular process that is required to produce proteins in cells that help us grow, develop and function.

Lead researcher, Professor Sureshkumar Balasubramanian of Monash University's School of Biological Sciences, said the finding allows researchers to link disease-associated genetic mutations that affect this process and develop suitable treatment options.

"This is not just hope, this is a clear explorable pathway to a cure for those who are living with some of the most debilitating and life-threatening conditions and diseases," said Professor Balasubramanian. "We expect scientists to begin using this finding right away to inform the development, and cures won't be too far behind that.

"What we are really excited about is that this allows for personalized therapeutic solutions for rare and under-researched genetic conditions and diseases, because we can now pinpoint exactly how they were caused."

mRNA, or messenger ribonucleic acids, are the key intermediates between DNA, the genetic blueprint, and proteins that carry out most of the work in our cells. RNA splicing ensures proper reading of the blueprint by removing some sections of the RNA, a bit like a book editor taking out unnecessary parts of a story to improve its quality.

Genetic mutations can modify RNA splicing, affecting processes like growth, development and response to external stimuli. Defective RNA splicing can result in serious and life-threatening genetic conditions and disease, including cancer.

The Monash-led research compared millions of splice-sites, the positions at which cutting and joining of RNA occurs, in plants before moving on to samples of more than 25 different species, including humans.

Professor Balasubramanian said the work was carried out using an innovative tool, SpliSER, developed by his team in 2021 to measure RNA splicing. "The tool works very effectively, subsequently allowing the assessment of the impact of genetic mutations. The SpliSER analysis simply worked like magic and the global patterns we saw were striking."

Professor Balasubramanian is already working to share his findings with groups who are working to address rarer diseases, including those that present in specific populations, including those that may be under-represented in worldwide genomic studies.