Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
Gene. 2013 Oct 10;528(2):360-3. doi: 10.1016/j.gene.2013.07.010. Epub 2013 Jul 24.
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.
P 体是参与 mRNA 沉默和降解的 100-300nm 大小的细胞器。据报道,共有 60 种人类蛋白质定位于 P 体。一些人类单核苷酸多态性通过改变蛋白质的结构和功能导致复杂疾病。此外,SNP 还改变了各种转录因子结合、剪接和 miRNA 调节位点。由于 P 体在 mRNA 调节中的重要功能,我们通过计算方法探索了 7 种 P 体成分(如 XRN1、DCP2、EDC3、CPEB1、GEMIN5、STAU1 和 TRIM71)中 SNP 的功能意义。利用 SIFT 等广泛使用的公共可用软件程序,对这些成分的非同义 SNP 进行了计算分析,随后是 PolyPhen、PANTHER、MutPred、I-Mutant-2.0 和 PhosSNP 1.0。利用 FastSNP 分析了调控区非编码 SNP 的功能意义。利用 miRSNP 数据库,我们研究了 SNP 在改变上述基因中 miRNA 结合位点的情况下的作用。我们的计算机研究已经确定了各种有害 SNP,这种编目是必要的,为进一步通过体外和体内方法进行分析提供了第一手信息,以更好地理解 P 体在健康和疾病中的维持、组装和功能方面。