题 目：Translation Of Circular RNAs As Drivers for Alzheimer’s Disease

主 讲：Stefan Stamm教授

时 间：2026年1月6日（周二）下午14:00-15:00

地 点：学习书坊

报告摘要：

Circular RNAs (circRNAs) are covalently closed, often human-specific RNAs. Increasing evidence shows that circRNAs can be translated, where most frequently RNA modifications such as m6A and inosine, promote ribosomal entry. We found that adenosine to inosine RNA modification result in the translation of circRNAs formed by the MAPT (microtubule associated protein tau) gene. mRNA-encoded MAPT proteins form neurofibrillary tangles (NFTs), the hallmark of Alzheimer’s disease (AD) and related tauopathies. The circRNA-encoded proteins promote aggregation of mRNA-encoded tau protein in vitro. RNA sequencing showed that during AD progression in entorhinal cortex the deamination of adenosines to inosines (A>I modification) of circular RNAs strongly correlates with Braak stages, i.e. AD severity, which was not observed for mRNA. Through a series of in vitro and in vivo studies, we propose the hypothesis that human-specific circRNAs from the MAPT-gene are translated in neurons after RNA modification, possibly caused by the inflammation leading to RNA editing through ADAR1-p150. The circRNA-protein products cause aggregation of mRNA-encoded tau protein leading to neuronal death. Thus, targeting circMAPT RNAs using siRNAs and/or blocking their translation could be a new therapeutic avenue for AD. 

个人简介：

Dr. Stefan Stamm is a Professor in the Department of Molecular and Cellular Biochemistry at the University of Kentucky College of Medicine. He received his MSc. degree and Ph.D from the University of Hannover. Dr. Stamm's research focuses on alternative pre-mRNA processing, including alternative splicing, RNA stability, and circular RNA biogenesis, with a strong emphasis on their roles in human diseases such as Alzheimer's disease and Prader-Willi syndrome. He leads the Stamm Laboratory, where his work advances the understanding of RNA regulation and its translational potential for therapeutic development, and he actively mentors MD/PhD trainees while contributing to interdisciplinary biomedical research.