{"id":2103,"date":"2025-09-06T00:16:08","date_gmt":"2025-09-06T00:16:08","guid":{"rendered":"https:\/\/www.newsbeep.com\/ie\/2103\/"},"modified":"2025-09-06T00:16:08","modified_gmt":"2025-09-06T00:16:08","slug":"how-quickly-mrna-degrades-is-linked-to-autoimmune-disease-risk","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ie\/2103\/","title":{"rendered":"How quickly mRNA degrades is linked to autoimmune disease risk"},"content":{"rendered":"

\"How<\/p>\n

Experimental support for asRS variants. Schematic illustration of MapUTR design. Credit: Nature Genetics (2025). https:\/\/doi.org\/10.1038\/s41588-025-02326-8<\/p>\n

A pizza shop with 30 delivery people ought to be able to deliver a lot of pizzas\u2014if their cars don’t break down on the way. Likewise, genes that produce a lot of messenger RNA (mRNA) molecules can build a lot of proteins\u2014if these molecules don’t fall apart before the job gets done.<\/p>\n

Inside almost every human cell is DNA, a comprehensive instruction manual for building and maintaining the body. Genes in that manual contain the instructions for making proteins. But those instructions must travel from the cell’s nucleus, where the DNA lives, to the outer region of the cell\u2014the cytoplasm\u2014where proteins are actually made.<\/p>\n

That’s where mRNA comes in. Like a messenger, it copies the instructions from the DNA in the nucleus and carries them out to the protein-making machinery. More mRNA typically means more protein\u2014unless the mRNA is unstable and breaks down too quickly.<\/p>\n

“Every mRNA has to die in the end,” says Xinshu Xiao, a professor of integrative biology and physiology at UCLA and senior author of a paper<\/a> published in Nature Genetics.<\/p>\n

“It’s produced, it does its job, and then it’s destroyed. But most research has focused on how mRNA is made. Much less attention has been paid towards how fast it’s degraded\u2014and that’s just as important.”<\/p>\n

Both the production and stability of mRNA can be affected by mutations in the DNA, which are commonly referred to as genetic variants. These variants can affect how much protein a cell makes, and in turn, influence a person’s risk of disease. But figuring out whether a variant affects how much mRNA is made\u2014or how long it survives\u2014has been a major challenge.<\/p>\n

Led by UCLA doctoral student Elaine Huang, Xiao’s team developed a computational tool called RNAtracker, which is freely available.<\/a> The software allows researchers to pinpoint whether a gene is being regulated through changes in mRNA production or in mRNA stability. In pizza terms: Is the problem that not enough pizzas are being made or that the delivery cars are breaking down? RNAtracker helps scientists trace the breakdown.<\/p>\n

The researchers applied RNAtracker to a publicly available dataset of 16 human cell<\/a> lines, in which newly made mRNAs had been chemically labeled and tracked over time. This allowed them to identify genes whose stability varies due to specific mutations. Many of these genes are involved in immune system function<\/a>\u2014especially the innate immune system, the body’s first line of defense against infections.<\/p>\n

The team also found that several of the genetic variants linked to unstable mRNA had already been associated with autoimmune diseases<\/a> in large-scale genetic studies.<\/p>\n

“One insight from this project is that some disease-associated variants may be acting through effects on mRNA stability,” said Xiao.<\/p>\n

Using additional modeling, the researchers linked expression levels of these stability-regulated genes to diseases including allergic rhinitis<\/a>, lupus, diabetes mellitus and multiple sclerosis. The findings suggest that mRNA stability\u2014long overlooked\u2014may be a key mechanism behind many immune-related diseases.<\/p>\n

“Basic research like ours shifts the paradigm of what people focus on,” said Huang. “For drug developers or researchers working on treatments, you can’t target what you don’t know is important. We are trying to bring attention to genetic variants that affect mRNA stability, which hasn’t gotten the spotlight it deserves.”<\/p>\n

“The NIH plays a critical role by supporting large-scale efforts like ENCODE,” said Xiao. “They make it possible for researchers around the world to access massive datasets and make discoveries like ours.”<\/p>\n

More information:
\n Huang, E., et al. Genetic variants affecting RNA stability influence complex traits and disease risk. Nature Genetics (2025). DOI: 10.1038\/s41588-025-02326-8<\/a> www.nature.com\/articles\/s41588-025-02326-8<\/a><\/p>\n

\t\t\t\t\t\t\t\t\t\t\t\tProvided by
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\tUniversity of California, Los Angeles<\/a>
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\t\t\t\t\t\t\t\t\t\t\t\t\t<\/a><\/p>\n

\n Citation:
\n How quickly mRNA degrades is linked to autoimmune disease risk (2025, September 5)
\n retrieved 5 September 2025
\n from https:\/\/medicalxpress.com\/news\/2025-09-quickly-mrna-degrades-linked-autoimmune.html\n <\/p>\n

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