ABSTRACT
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), preferentially 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, "AA" dinucleotide was the most common CS (37.5%) associated with this set of genes. Approximately 90% of CPGs exhibited evidence of alternative polyadenylation (more than one functional PAS). Finally, the mir-192 family was significantly overrepresented as regulator of tumor suppressor genes (Pâ¯<â¯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 molecular analyses covering these frequently neglected regulatory sequences.
Subject(s)
Genetic Predisposition to Disease , MicroRNAs/metabolism , Neoplasms/genetics , Poly A/chemistry , Polyadenylation , 3' Untranslated Regions , Binding Sites , Cell Line, Tumor , Computer Simulation , Humans , MicroRNAs/genetics , Neoplasms/metabolism , Nucleotides/genetics , Oncogenes , RNA Precursors , Signal TransductionABSTRACT
PURPOSE: The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. METHODS: This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. RESULTS: Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. CONCLUSIONS: We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.
