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 (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 molecular analyses covering these frequently neglected regulatory sequences.
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http://dx.doi.org/10.1016/j.gene.2019.143943 | DOI Listing |
Biology (Basel)
December 2024
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan 430072, China.
Alternative splicing of (DEAD-box helicase 4), a key germline marker gene, has been reported to generate sex-specific transcripts in zebrafish gonads. The biological functions and regulatory mechanisms of the ovary-specific transcript () during oogenesis remain unclear. In this study, we found that mutants, in which was specifically deleted, had enlarged ovaries but laid fewer eggs, along with having a lower fertilization rate compared to WT controls.
View Article and Find Full Text PDFChembiochem
November 2024
Modality Research Laboratories 1, Research Unit, Research Division, Kyowa Kirin Co., Ltd., 3-6-6 Asahi, Machida, Tokyo, 194-8533, Japan.
Position-specific nucleoside sugar modifications have been shown to improve the translational activity and stability of chemically synthesized mRNA. For pharmaceutical applications of chemically modified mRNAs, a rapid purification methodology is imperative to identify the optimal modification pattern. However, while the chemical synthesis of mRNAs can be accomplished by splint ligation of oligonucleotide fragments, the current purification method for ligated mRNAs based on denaturing polyacrylamide gel electrophoresis tends to be time consuming.
View Article and Find Full Text PDFHum Mol Genet
November 2024
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States.
Alternative polyadenylation (APA) is a major mechanism of post-transcriptional regulation that affects mRNA stability, localization and translation efficiency. Previous pan-cancer studies have revealed that APA is frequently disrupted in cancer and is associated with patient outcomes. Yet, little is known about cancer type-specific APA alterations.
View Article and Find Full Text PDFMol Cell
November 2024
Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:
The export and degradation pathways compete to sort nuclear RNAs, yet the default pathway remains unclear. Sorting of mature RNAs to degradation, facilitated by the exosome co-factor poly(A) exosome targeting (PAXT), is particularly challenging for their resemblance to mRNAs intended for translation. Here, we unveil that ZFC3H1, a core PAXT component, is co-transcriptionally loaded onto the first exon/intron of RNA precursors (pre-RNAs).
View Article and Find Full Text PDFMicrob Genom
October 2024
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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