Electronic Thesis and Dissertation Repository

Expression and subcellular localization of circRNAs dysregulated ALS that are encoded in cytoskeletal protein genes

Asieh Alikhah, The University of Western Ontario

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder that causes the death of motor neurons. While alterations in the metabolism of RNA, including RNA-binding proteins have been linked to the pathogenesis of ALS, our understanding of the role of non-coding RNAs including circRNAs is less well developed. In this study, using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence (IF) with markers of RNP granules, I investigated the effect of osmotic stress on the localization and expression of a selection of circRNAs whose expression is dysregulated in ALS. Alteration in the number of granules for two circRNAs was observed in HEK293T cells under osmotic stress. I also have observed that circRNAs are present in RNP granules under a stress condition. This finding is consistent with the hypothesis that circRNAs might participate in the biology of ribonucleprotein (RNP) granules under pathological conditions such as those observed in ALS.