title: Exploration of deleterious single nucleotide polymorphisms in the components of human P bodies: an in silico approach.
abstract: P bodies are 100-300 nm sized organelles involved in mRNA silencing and degradation. A total of 60 human proteins have been reported to localize to P bodies. Several human SNPs contribute to complex diseases by altering the structure and function of the proteins. Also, SNPs alter various transcription factors binding, splicing and miRNA regulatory sites. Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71. Computational analyses of non-synonymous SNPs of these components was initiated using well utilized publicly available software programs such as the SIFT, followed by PolyPhen, PANTHER, MutPred, I-Mutant-2.0 and PhosSNP 1.0. Functional significance of noncoding SNPs in the regulatory regions were analysed using FastSNP. Utilizing miRSNP database, we explored the role of SNPs in the context that alters the miRNA binding sites in the above mentioned genes. Our in silico studies have identified various deleterious SNPs and this cataloguing is essential and gives first hand information for further analysis by in vitro and in vivo methods for a better understanding of maintenance, assembly and functional aspects of P bodies in both health and disease.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Thejaswini
authors.initials: T
authors.lastname: Venkatesh
authors.forename: Padmanaban S
authors.initials: PS
authors.lastname: Suresh
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics; D005095:Exoribonucleases / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics; D015388:Organelles / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D055532:SMN Complex Proteins; D014157:Transcription Factors / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: C490386:CPEB1 protein, human; D003598:Cytoskeletal Proteins; C525042:EDC3 protein, human; C449808:GEMIN5 protein, human; D008869:Microtubule-Associated Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C492185:STAU1 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; C584142:TRIM71 protein, human; D044767:Ubiquitin-Protein Ligases; D004722:Endoribonucleases; D005095:Exoribonucleases; C470512:XRN1 protein, human; C467723:DCP2 protein, human
keywords: 5′-3′ exoribonuclease 1; CPEB1; DCP2; DCP2 decapping enzyme homolog [S. cerevisiae]); EDC3; P bodies; PANTHER; Protein ANalysis THrough Evolutionary Relationships; SIFT; SNP; STAU1; TRIM71; UTR; XRN1; cytoplasmic polyadenylation element binding protein 1; enhancer of mRNA decapping 3 homolog [S. cerevisiae]); miRNA; micro ribonucleic acid; non-synonymous; ns; reference SNP; rs; single nucleotide polymorphism; sorting intolerant from tolerant; staufen, RNA binding protein, homolog 1 [Drosophila]); subPSEC; substitution position-specific evolutionary conservation; tripartite motif containing 71, E3 ubiquitin protein ligase; untranslated region