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  • br Igor Araujo Vieiraa b Mariana

    2019-10-01


    Igor Araujo Vieiraa,b, , Mariana Recamonde-Mendozac,d, Vandeclecio Lira da Silvae, Delva Pereira Leãoa,d, Marina Roberta Scheidb,f, Sandro José de Souzae,g,h, Patricia Ashton-Prollaa,b,f,i,j a Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil b Laboratório de Medicina Genômica, Serviço de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil c Instituto de Informática, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil d Núcleo de Bioinformática, Serviço de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil e Programa de Pós-Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil f Programa de Pós-graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil g Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil h Bioinformatics Multidisciplinary Environment, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil i Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil j Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
    Keywords:
    Polyadenylation
    Polyadenylation sequences
    microRNAs
    Gene T-5224 regulation
    Cancer predisposition genes 
    Two core polyadenylation elements (CPE) located in the 3′ untranslated region of eukaryotic pre-mRNAs play an essential role in their processing: the polyadenylation signal (PAS) AAUAAA and the cleavage site (CS), pre-ferentially a CA dinucleotide. Herein, we characterized PAS and CS sequences in a set of cancer predisposition genes (CPGs) and performed an in silico investigation of microRNAs (miRNAs) regulation to identify potential tumor-suppressive and oncogenic miRNAs. NCBI and alternative polyadenylation databases were queried to characterize CPE sequences in 117 CPGs, including 81 and 17 known tumor suppressor genes and oncogenes, respectively. miRNA-mediated regulation analysis was performed using predicted and validated data sources. Based on NCBI analyses, we did not find an established PAS in 21 CPGs, and verified that the majority of PAS already described (74.4%) had the canonical sequence AAUAAA. Interestingly, T-5224  “AA” dinucleotide was the most common CS (37.5%) associated with this set of genes. Approximately 90% of CPGs exhibited evidence of al-ternative polyadenylation (more than one functional PAS). Finally, the mir-192 family was significantly over-represented as regulator of tumor suppressor genes (P < 0.01), which suggests a potential oncogenic function. Overall, this study provides a landscape of CPE in CPGs, which might be useful in development of future mo-lecular analyses covering these frequently neglected regulatory sequences.
    1. Introduction
    Polyadenylation, which comprises the pre-mRNA cleavage followed by adding a stretch of adenosine residues (called poly(A) tail) to the 3′ end, is an essential nuclear step during pre-mRNAs processing in almost all eukaryotic cells (Zhao et al., 1999; Millevoi and Vagner, 2010). Three
    cis-acting RNA sequence elements often termed as the “core” poly-adenylation elements (CPE) determine precisely the 3′ end cleavage/ polyadenylation site in mammalian pre-mRNAs: (1) the poly(A) signal (PAS), a highly conserved hexamer AAUAAA or its close variants; (2) the de facto polyadenylation site or cleavage site (CS), preferentially a “CA” dinucleotide located 10–30 nucleotides (nt) downstream of the PAS; and