title: An in-depth map of polyadenylation sites in cancer.
abstract: We present a comprehensive map of over 1 million polyadenylation sites and quantify their usage in major cancers and tumor cell lines using direct RNA sequencing. We built the Expression and Polyadenylation Database to enable the visualization of the polyadenylation maps in various cancers and to facilitate the discovery of novel genes and gene isoforms that are potentially important to tumorigenesis. Analyses of polyadenylation sites indicate that a large fraction (∼30%) of mRNAs contain alternative polyadenylation sites in their 3' untranslated regions, independent of the cell type. The shortest 3' untranslated region isoforms are preferentially upregulated in cancer tissues, genome-wide. Candidate targets of alternative polyadenylation-mediated upregulation of short isoforms include POLR2K, and signaling cascades of cell-cell and cell-extracellular matrix contact, particularly involving regulators of Rho GTPases. Polyadenylation maps also helped to improve 3' untranslated region annotations and identify candidate regulatory marks such as sequence motifs, H3K36Me3 and Pabpc1 that are isoform dependent and occur in a position-specific manner. In summary, these results highlight the need to go beyond monitoring only the cumulative transcript levels for a gene, to separately analysing the expression of its RNA isoforms.
authors: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors: Yuefeng
authors: Y
authors: Lin
authors: Zhihua
authors: Z
authors: Li
authors: Fatih
authors: F
authors: Ozsolak
authors: Sang Woo
authors: SW
authors: Kim
authors: Gustavo
authors: G
authors: Arango-Argoty
authors: Teresa T
authors: TT
authors: Liu
authors: Scott A
authors: SA
authors: Tenenbaum
authors: Timothy
authors: T
authors: Bailey
authors: A Paula
authors: AP
authors: Monaghan
authors: Patrice M
authors: PM
authors: Milos
authors: Bino
authors: B
authors: John
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D026723:Polyadenylation; D059368:RNA Isoforms / Q000737:chemistry / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D017423:Sequence Analysis, RNA
chemical_list: D020413:3' Untranslated Regions; D059368:RNA Isoforms; D022661:RNA, Untranslated; D038621:Regulatory Sequences, Ribonucleic Acid