Date: 2025-03-03
Proper gene expression relies on finely tuned RNA stability, yet its regulatory mechanisms remain unclear. Dr. Chien-Ling Lin’s group at the Institute of Molecular Biology employed massively parallel reporter assays to dissect the regulatory rules of RNA degradation systematically. Statistical modeling by Dr. Yen-Tsung Huang’s team at the Institute of Statistical Sciences revealed that exposure of UA dinucleotides drives RNA degradation. Consistently, fast-turnover genes, such as those regulating innate immunity and appetite, exhibit high UA-dinucleotide ratios in their untranslated regions (UTRs), and mutations that increase UA content reduce RNA half-life. This simple rule may serve as a screening tool for UTR mutation-mediated pathologies and guide the design of synthetic RNAs for therapeutic applications.
This study was published in eLife in February 2025, with first authors Dr. Jia-Ying Su, TIGP-BIO recent graduate, and Yun-Lin Wang, IMB research assistant. This study was funded by the Career Development Award and Multidisciplinary Health Cloud Research Program of Academia Sinica, National Science and Technology Council, and National Health Research Institutes.