Title: In-silico analysis for RNA-interference mechanism of α-synuclein to treat Parkinson's disease

Authors: S. Seema; R. Seenivasagam; K. Hemavathi

Addresses: Department of Bioinformatics, University of East London, Docklands Campus, University Way, London E16 2RD, UK ' Division of Drug Discovery and Development, Center of Molecular and Computational Biology, Department of Botany, St. Joseph's College, P.B. 27094, 36, Langford Road, Bangalore, Karnataka 560027, India ' Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur – 613 402, Tamil Nadu, India

Abstract: Parkinson's Disease (PD) causing mutations in α-synuclein gene are ALA30PRO, GLU46LYS and ALA53THR. The conformational changes in proteins with respect to all the three mutations were analysed. These were used to predict the structures of Short Interfering RNA (siRNA) antisense strand and siRNA region. The siRNA binds with the argonaute protein forming RNA Induced Silencing Complex (RISC). Then, siRNA antisense-strand was attached to RISC. The structure of dicer (RNase-III-enzyme) cleaves double-stranded RNA (dsRNA) into two siRNA-strands. Incorporation of single siRNA-strand into RISC guides to pair with the complementary α-synuclein target-messenger RNA (mRNA) thereby enabling it to cleave the target.

Keywords: antisense RNA; RNA interference; structural biology; molecular structure; gene silencing; alpha-synuclein; PD; Parkinson's disease; RNA biotools; molecular neuroscience; bioinformatics; proteins; protein conformational changes; short interfering RNA; siRNA.

DOI: 10.1504/IJBRA.2013.056630

International Journal of Bioinformatics Research and Applications, 2013 Vol.9 No.6, pp.557 - 575

Available online: 30 Sep 2013 *

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