In silico analysis of COSMIC retrieved P body gene mutations in breast cancer

Abstract

P bodies (Processing bodies) are mRNP granules and are involved in mRNA decay, gene silencing by miRNA or siRNA, deadenylation and decapping. These are dynamic and shuttle their components with stress granules, ribosomes and stalled mRNAs within them can assemble to polysomes. Research suggests that several components of stress granules and P bodies contribute to carcinogenesis. In corroboration, COSMIC (catalogue of somatic mutations in cancer) database documents somatic mutations of P body genes. In our study, we have retrieved the somatic mutations from COSMIC for critical P body genes such as DCP1B, EIF4E, XRN1, MOV10, CNOT6, HTT and GEMIN5 and examined for their deleteriousness using various online tools such as PolyPhen, MutationTaster and STRUM. A total of 5, 2, 17, 11, 8, 22 and 15 breast cancer mutations were retrieved for DCP1B, EIF4E, XRN1, MOV10, CNOT6, HTT and GEMIN5 respectively. Of these, our analysis has identified 18 mutations (DCP1B-1, EIF4E-1, MOV10-1, GEMIN5-2, CNOT6-2, HTT-9 and XRN1-2) to be deleterious. Also, our 3D molecular dynamic studies suggest that HTT and EIF4E mutations induce perturbations in the mutant proteins. P body dynamics are marked by interactions between P body proteins and other cellular components and our results give insights to examine the P body dynamics on such mutation landscapes.