![]() ![]() Intronic polyadenylation of Pdgfra produces a truncated protein that inhibits PDGF signaling and protects mice from fibrosis ( Mueller et al. Cancer cells use aberrant intronic pA sites more frequently than normal cells, and the partial loss of function of tumor suppressor genes (TSGs) caused by IpA can contribute crucially to tumorigenesis ( Lee et al. For example, IpA diversifies immune cell proteomes via loss of the C-terminal domain ( Singh et al. Recent studies have begun to highlight the biological significance of IpA. 2018), CR-APA and IpA are less prevalent and their biological functions are not well understood. Although UTR-APA is widespread and involved in diverse biological processes ( Mayr and Bartel 2009 Chen et al. Both CR-APA and IpA introduce a premature termination signal and lead to changes in either the coding sequence or the 3′ UTR of the corresponding mRNA ( Tian et al. 2013 Berkovits and Mayr 2015 Tian and Manley 2017). ![]() UTR-APA changes the length of 3′ UTR, thereby altering RNA stability, translation efficiency, RNA localization, or even protein localization ( Elkon et al. There are different types of APA based on the location of the polyadenylation (pA) site in an mRNA, such as 3′ untranslated region APA (UTR-APA), coding region APA (CR-APA), and intronic polyadenylation (IpA) ( Tian and Manley 2017). In summary, IPAFinder enables the global discovery and characterization of biologically regulated IpA with standard RNA-seq data and should reveal the biological significance of IpA in various processes.Īlternative polyadenylation (APA) of mRNA is a widespread phenomenon in diverse species, serving as an important contributor to transcriptome diversity ( Elkon et al. Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and m 6A modification. Applying IPAFinder to 256 pan-cancer tumor/normal pairs across six tumor types, we discovered 490 recurrent dynamically changed IpA events, some of which are novel and derived from cancer-associated genes such as TSC1, SPERD2, and CCND2. ![]() Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. ![]()
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