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

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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.

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Acknowledgements

We are thankful of Caenorhabditis Genetics Center (CGC), University of Minnesota, MN, USA, for providing the C. elegans strains. CSIR-CDRI communication number is 9614.

Funding

CGC is funded by the NIH National Center for Research Resources (NCRR). LK is supported by Senior Research Fellowship from Council for Scientific and Industrial Research (CSIR), and S, HR, and SS are supported by Senior Research Fellowship from UGC. AN acknowledges financial support from CSIR and DST, Government of India.

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  1. Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, UP, 226 031, India

    Lalit Kumar,  Shamsuzzama, Pooja Jadiya, Rizwanul Haque, Shikha Shukla & Aamir Nazir

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  1. Lalit Kumar
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  2. Shamsuzzama
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LK conducted the experiments, analyzed the data, and wrote the manuscript; S, JP, HR, and SS conducted the experiments. AN conceived the study, analyzed the data, wrote the manuscript, and provided reagents and support.

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Correspondence to Aamir Nazir.

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Kumar, L., Shamsuzzama, Jadiya, P. et al. Functional Characterization of Novel Circular RNA Molecule, circzip-2 and Its Synthesizing Gene zip-2 in C. elegans Model of Parkinson’s Disease. Mol Neurobiol 55, 6914–6926 (2018). https://doi.org/10.1007/s12035-018-0903-5

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