A new computational tool developed by UCLA researchers sheds light on how mRNA stability affects protein production and contributes to immune-related diseases.
Imagine a pizza shop with 30 delivery drivers. The shop can produce many pizzas, but if the cars break down, the pizzas never reach customers. Similarly, genes in human cells can produce many messenger RNA (mRNA) molecules, but if these molecules degrade too quickly, the proteins they encode may never be made.
The Role of mRNA in Protein Production #
Inside each human cell, DNA serves as the instruction manual for building and maintaining the body. Genes in the DNA encode proteins, but the instructions must travel from the nucleus to the cytoplasm, where proteins are synthesized.
Here, mRNA acts as the messenger, copying instructions from DNA and delivering them to protein-making machinery. The quantity and stability of mRNA directly influence how much protein a cell produces.
“Every mRNA has to die in the end,” said Xinshu Xiao, professor of integrative biology and physiology at UCLA. “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 — and that’s just as important.”
RNAtracker: A Tool to Study mRNA Stability #
Mutations in DNA, known as genetic variants, can impact both mRNA production and mRNA stability, ultimately affecting disease risk. Determining whether a variant influences mRNA creation or degradation has been a major challenge.
Led by UCLA doctoral student Elaine Huang, Xiao’s team developed RNAtracker, a freely available computational tool that identifies whether gene regulation occurs through mRNA production or stability. In our pizza analogy, it determines whether the problem is too few pizzas being made or broken delivery cars.
Using a dataset of 16 human cell lines with newly labeled mRNAs, the researchers pinpointed genes whose stability is altered by specific mutations. Many of these genes were involved in innate immune system function, the body’s first line of defense against infections.
Linking mRNA Stability to Immune Diseases #
Several of the variants associated with unstable mRNA were already linked to autoimmune diseases in prior genetic studies. Additional modeling connected expression levels of stability-regulated genes to conditions such as:
- Allergic rhinitis
- Lupus
- Diabetes mellitus
- Multiple sclerosis
“One insight from this project is that some disease-associated variants may be acting through effects on mRNA stability,” said Xiao.
These findings highlight mRNA stability as a key mechanism behind many immune-related diseases, a factor long overlooked in genetic research.
Implications for Research and Drug Development #
“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.”
The study was supported by the National Institutes of Health (NIH) and utilized publicly available data from ENCODE, an NIH-backed consortium.
“The NIH plays a critical role by supporting large-scale efforts like ENCODE,” Xiao added. “They make it possible for researchers worldwide to access massive datasets and make discoveries like ours.”
Conclusion #
By revealing how mRNA stability influences protein production and contributes to immune-related diseases, the UCLA team provides researchers with a new tool for exploring genetic mechanisms. RNAtracker may guide future drug development and deepen our understanding of autoimmune and inflammatory diseases.
Additional Authors: Ting Fu, Ling Zhang, Guan’ao Yan, Ryo Yamamoto, Sari Terrazas, Thuy Linh Nguyen, Carlos Gonzalez-Figueroa, Armen Khanbabaei, Jae Hoon Bahn, Rajagopal Varada, Kofi Amoah, Jonatan Hervoso, Michelle Paulsen, Brian Magnuson, Mats Ljungman, Jingyi Jessica Li.