Good news! This is early, but promising research!
"Key takeaways
- Messenger RNA copies and carries instructions from the DNA in the cell’s nucleus to where protein is made. More mRNA usually means more protein — unless the mRNA is unstable and breaks down too quickly.
- Mutations in the DNA can affect the production and stability of mRNA, which influences how much protein a cell produces and a person’s risk of disease.
- UCLA researchers have identified genetic mutations that influence mRNA stability. Many of these genes are involved in immune system function.
... [mRNA] is 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 — and that’s just as important.”
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 — or how long it survives — has been a major challenge. ...
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. ...
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. ..."
From the abstract:
"Gene expression is modulated jointly by transcriptional regulation and messenger RNA stability, yet the latter is often overlooked in studies on genetic variants. Here, leveraging metabolic labeling data (Bru/BruChase-seq) and a new computational pipeline, RNAtracker, we categorize genes as allele-specific RNA stability (asRS) or allele-specific RNA transcription events.
We identify more than 5,000 asRS variants among 665 genes across a panel of 11 human cell lines.
These variants directly overlap conserved microRNA target regions and allele-specific RNA-binding protein sites, illuminating mechanisms through which stability is mediated.
Furthermore, we identified causal asRS variants using a massively parallel screen (MapUTR) for variants that affect post-transcriptional mRNA abundance, as well as through CRISPR prime editing approaches.
Notably, asRS genes were enriched significantly among a multitude of immune-related pathways and contribute to the risk of several immune system diseases. This work highlights RNA stability as a critical, yet understudied mechanism linking genetic variation and disease."
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