A pizza shop with 30 delivery people ought to be able to deliver a lot of pizzas—if 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—if these molecules don't fall apart before the job gets done.

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—the cytoplasm—where proteins are actually made.

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—unless the mRNA is unstable and breaks down too quickly.

The team also found that several of the genetic variants linked to unstable mRNA had already been associated with autoimmune diseases in large-scale genetic studies.

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

Using additional modeling, the researchers linked expression levels of these stability-regulated genes to diseases including allergic rhinitis, lupus, diabetes mellitus and multiple sclerosis. The findings suggest that mRNA stability—long overlooked—may be a key mechanism behind many immune-related diseases.