Page 29 - IBRO_RNA School_Abstract Book

Role of CAG RNA in neuroinflammation in polyglutamine

disease

Aksheev Bhambri

University of Texas, Texas, U.S

Polyglutamine diseases is a class of neurodegenerative diseases that occur due
to expansion of CAG triplet repeats resulting in an expanded glutamine tract in the
protein. This causes protein instability and accumulation leading to apoptosis of the
cells. Recent studies have shown that CAG repeat containing RNA expressed during

polyglutamine diseases can bind and sequester proteins affecting their function,
thereby leading to cell death. In a previous study, we showed interferon released
by neuronal cells during polyglutamine protein accumulation. We hypothesized that
CAG RNA may bind to proteins in the neuronal cells and this binding may trigger
interferon release by the cells. We found 60 proteins capable of binding CAG RNA while 7
proteins were found to preferentially associate with expanded CAG RNA. Moreover,
neuronal cells expressing polyglutamine protein showed upregulation of RNA sensors
as well as upregulation of critical transcription factor, IRF3, involved in RNA-mediated
inflammation pathway. However, on further investigation we find that CAG RNA is not
sufficient to induce interferon release or cause apoptosis of neuronal cells. Hence,
we find that CAG RNA may alter protein function and/or homeostasis in polygluta-

mine disease but is not involved directly in interferon release by the neuronal cells.