Circular RNAs regulate its parental genes transcription in the AD mouse model using two methods of library construction.

Circular RNA (circRNA) is an important class of noncoding RNA. Current, protocols to detected circRNAs have utilized nonpolyadenylated RNAs, ribosomal RNA-depleted RNA samples (rRNA- library), and rRNA-depleted RNA that has been treated with RNase R to digest linear RNA (rRNA- RNase R+ library). Accumulating evidence suggests the participation of circRNAs in Alzheimer's disease (AD)-associated pathophysiology, but the details remain largely unknown. Here, we elucidated the brain circRNAs profiles of AD-model and WT mice using two methods of library construction (rRNA- RNase R+ libraries and rRNA- libraries). We focused on the construction of libraries that best allow the identification of circRNAs from next-generation RNA sequencing data. We obtained a significantly higher abundance of circRNAs in the rRNA- RNase R+ libraries than in the rRNA- libraries. Additionally, the rRNA- RNase R+ libraries more clearly revealed differentially expressed circRNAs. We performed a correlation analysis between differentially expressed circRNAs and their parental genes and performed KEGG analysis of the parental genes to explore the role of circRNA in AD. Our results identified significantly dysregulated circRNAs and KEGG analysis revealed that the identified circRNAs are involved in regulating AD development from distinct origins, including cAMP signaling, MAPK signaling, insulin secretion, Axon guidance, Long-term potentiation, dopaminergic synapse, and ErBb signaling pathways. Following rigorous selection, we identified several important circRNAs and mRNAs and propose the circRNAs regulate parental gene transcription or affect variable splicing, which were discovered to be mainly involved in Aβ production and cognitive performance (TRPC6) and neuronal differentiation and development (NME7). These newly identified circRNAs should serve as a valuable resource for the future development of potential biomarkers and therapeutic targets for AD. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Citation

Nana Ma, Changrui Tie, Bo Yu, Wei Zhang, Jun Wan. Circular RNAs regulate its parental genes transcription in the AD mouse model using two methods of library construction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020 Aug;34(8):10342-10356

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PMID: 32530085

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