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Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq).
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In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.Īn emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. We also describe next-generation sequencing methods and computational tools for use in poly(A) signal detection and APA repositories and databases. We focus particularly on the interaction of APA with microRNAs, RNA binding proteins and other related factors, the core pre-mRNA 3’end processing complex, and 3’UTR length change.
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Here, we provide an overview of four types of APA and their impacts on gene regulation. Recent studies have revealed various APA regulatory mechanisms that promote the development and progression of a number of human diseases, including cancer. APA is frequently dysregulated in cancers leading to changes in oncogenes and tumor suppressor gene expressions. As a key molecular mechanism, APA is involved in various gene regulation steps including mRNA maturation, mRNA stability, cellular RNA decay, and protein diversification. Occurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3’ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene. The curves correspond to the distance distribution between the location of a given polyadenylation site and the nearest regulatory mark (H3K36Me3, Pol2, Pabpc1 and Elav1), as inferred using Chip-Seq/RIP-Seq. (B and C) Chip-Seq/RIP-Seq data comparisons of H3K36Me3 and Pabpc1 to their functional analogs (Pol2 and Elav1) in identical cell lines (B: HepG2, C: GM12878) suggest preferential marking of polyadenylation sites of short isoforms by H3K36Me3 and Pabpc1. Readily noticeable locational preferences of the consensus motif, visible as peaks (arrows), are generally within ☒0 nts of the polyadenylation sites. (A) Motifs that are preferentially located near polyadenylation sites (position 0), and are more prevalently used by either short (red) or long (blue) isoform. (A–C) A total of 3270 genes containing both long and short forms that are genomically separated by at least 100 nts at their 3′ ends are used for the analysis. Polyadenylation maps enable the identification of isoform-dependent regulatory marks.