title: In silico characterization of a RNA binding protein of cattle filarial parasite Setaria digitata.
abstract: Human lymphatic filariasis (HLF) is a neglected tropical disease which threatens nearly 1.4 billion people in 73 countries worldwide. Wuchereria bancrofti is the major causative agent of HLF and it closely resembles cattle filarial parasite Setaria digitata. Due to difficulties in procuring W. bancrofti parasite material, S. digitata cDNA library has been constructed to identify novel drug targets against HLF and many of the cDNA sequences are yet to be assigned structure and function. In this study, a 549 bp long cDNA (sdrbp) has been sequenced and characterized in silico. The shortest ORF of 249 bp from the isolated cDNA encodes a polypeptide of 82 amino acids and shows an amino acid identity of 54% with the RRM domain of human cleavage stimulation factor-64 kDa subunit (CstF-64). Structure of the protein (sdRBP) obtained by homology modelling using RRM of CstF-64 as template adopts classical RRM topology (β1α1β2β3α2β4). sdRBP model built was validated by superimposition tools and Ramachandran plot analysis. CstF-64 plays an important role in pre-mRNA polyadenylation by interacting with specific GU-rich downstream sequence element. Molecular docking studies of sdRBP with different RNA molecules revealed that sdRBP has greater binding affinity to GU-rich RNA and comparable results were obtained upon similar docking of RRM of CstF-64 with the same RNA molecules. Therefore, sdRBP is likely to perform homologous function in S. digitata. This study brings new dimensions to the functional analysis of RNA binding proteins of S. digitata and their evaluation as new drug targets against HLF.
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
authors.forename: Nirupa
authors.initials: N
authors.lastname: Nagaratnam
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
authors.forename: Eric Hamilton
authors.initials: EH
authors.lastname: Karunanayake
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
authors.forename: Kamani Hemamala
authors.initials: KH
authors.lastname: Tennekoon
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
authors.forename: Sameera Ranganath
authors.initials: SR
authors.lastname: Samarakoon
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
authors.forename: Karthika
authors.initials: K
authors.lastname: Mayan
keywords: Cleavage stimulation factor; GU-rich downstream sequence element; Molecular docking; RRM domain; Ramachandran plot; pre-mRNA polyadenylation; superimposition