Functional Characterization of Novel Circular RNA Molecule, circzip-2 and Its Synthesizing Gene zip-2 in C. elegans Model of Parkinson’s Disease

TLDR: Employing transgenic C. elegans model of PD, RNase R-mediated cleavage of linear RNA followed by divergent primer-based amplifications are used towards identifying circzip-2, a novel circRNA molecule, which is synthesized from functionally important gene zip-2.

Abstract: Circular RNAs (circRNAs) are peculiar non-coding RNA molecules which are known to be present across taxa. Considering the body of evidence that establishes critical functions of non-coding RNA molecules, we endeavored to study circRNAs in the context of Parkinson’s disease (PD). Employing transgenic C. elegans model of PD, we used RNase R-mediated cleavage of linear RNA followed by divergent primer-based amplifications towards identifying circzip-2, a novel circRNA molecule. We went on to sequence circzip-2 which is synthesized from functionally important gene zip-2. Studying RNAi-induced knockdown conditions of zip-2, we observed a reduced aggregation of α-synuclein protein along with an enhanced lifespan of the worms. We further carried out transcriptome analysis of zip-2 silenced worms, which suggested that zip-2 might be functioning via Daf-16 pathway. Further interaction studies revealed that circzip-2 possibly sponges microRNA molecule miR-60 towards asserting an important role in various processes associated with PD.