Researchers investigating the genetics underlying the airway inflammation seen in severe asthma have, for the first time, discovered that proteins that bind to RNA are dysregulated, and drive changes in gene expression in the cells that line the airways.
Asthma is one of the most common chronic respiratory diseases. More common in children than adults, it’s often defined as an inflammatory disease, implying an immune-related component.
The inflammatory process that causes asthma is well understood, but not the genetics that drive it. Now, for the first time, a new study led by researchers at King’s College London has revealed the important role RNA and the proteins it regulates play.
The researchers obtained RNA genetic data from the cells of patients with and without asthma. RNA allows the transport and interpretation of genetic code within DNA. Messenger RNA (mRNA) carries protein information from the DNA in a cell’s nucleus to the cell’s cytoplasm or fluid interior. RNA-binding proteins bind to mRNAs selectively, localize them in subcellular compartments and regulate protein synthesis.
They found that two RNA-binding proteins, ZFP36L1 and ZFP36L2, were significantly dysregulated in asthmatics. When both proteins were restored in the bronchial epithelial cells of patients with severe asthma, the researchers observed a change in the expression of genes that control severe inflammation. They concluded that ZFP36L1 and ZPF36L2 drove changes in gene expression in epithelial cells in asthmatics.
In mice exposed to house dust mites to induce asthma-like symptoms, the researchers found that the proteins were mislocalized in the mice’s airway cells. Unlike proteins that have been localized into a subcellular compartment, mislocalized proteins can’t function normally. From this finding, the researchers suggest that mislocalized proteins contribute to the inflammation that characterizes asthma by performing different functions in the cell.
While the current study shows that the regulation of mRNA expression is a fundamental process underlying asthma, further research is needed to confirm the role of these RNA proteins in humans and better understand their impact on respiratory health.
The study was published in the journal Frontiers in Cell and Developmental Biology.
Source: King’s College London