Poster abstracts

Poster number 102 submitted by Megan Van Horn

The role of circular RNA in Parkinson’s disease etiology

Megan L. Van Horn (Carnegie Mellon University), Erika Kim (Carnegie Mellon University), Anna M. Kietrys (Carnegie Mellon University)

Abstract:
The world’s population is ageing, and this phenomenon correlates with a growing number of people diagnosed with neuronal disorders1. One of these late-onset diseases is Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide. Parkinsonism affects more than 1 million people in North America and over 60,000 new cases are identified every year2. Despite the effort of many research groups, very little is known about where and why neuronal degradation starts. To propose and develop an effective therapy for PD, we first need to understand the etiology of neurodegeneration.

Our group targets the problem of RNA-driven neurodegeneration and proposes new therapeutic approaches. Utilizing a high-throughput differential analysis of PD transcriptomes, we have identified circular RNA (circRNA) molecular markers that correlate with ageing and parkinsonism. Circular RNAs, because of their extended life span3 and a versatile interaction with small RNAs4,5 and proteins, are a strong candidate as cellular regulators of neurodegeneration3,5.

To identify potential novel circRNAs correlated with Parkinson’s disease stages, we analyzed multiple RNA-seq data sets collected from human specimens. The first set of data (control = 44, PD = 29) has shown a circRNA originating from chromosome 1 in the NBPF1 coding region. This underexpressed chr1 circRNA was found to have 97 potential miRNA binding sites and multiple associated RNA-binding proteins. These include EIF4A3, FMRP, and SFRS1, which are all linked to translation and splicing regulation, indicating this circRNA as a potential translation or alternative splicing influencer. In the same data set, PD samples showed significant overexpression of a mitochondrial circRNA originating from the COX3 coding region. This previously unknown circRNA possesses 21 potential miRNA binding sites. Both of these circRNAs have been experimentally found to be expressed in HEK293T and U87MG cells. We believe these identified circRNAs may trigger the neuron degeneration process and in the future be utilized as therapeutic targets.

References:
1. Tran J, Anastacio H, Bardy C. npj Park Dis. 2020. doi:10.1038/s41531-020-0110-8
2. Marras C, Beck JC, Bower JH, et al. npj Park Dis 2018. doi:10.1038/s41531-018-0058-0
3. Piwecka M, Glažar P, Hernandez-Miranda LR, et al. Science 2017. doi:10.1126/science.aam8526
4. Hansen TB, Jensen TI, Clausen BH, et al. Nature 2013. doi:10.1038/nature11993
5. Memczak S, Jens M, Elefsinioti A, et al. Nature 2013. doi:10.1038/nature11928

Keywords: circular RNA, Parkinsons disease, neurodegeneration