Polyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3′-untranslated region (3′-UTR) specific sequence signal. APA processing can generate several mRNA isoforms from a single gene, which may have different biological functions on their target gene. As a result, cellular genomic stability, proliferation capability, and transformation feasibility could all be affected. Furthermore, APA modulation regulates disease initiation and progression. APA status could potentially act as a biomarker for disease diagnosis, severity stratification, and prognosis forecast. While the advance of modern throughout technologies, such as next generation-sequencing (NGS) and single-cell sequencing techniques, have enriched our knowledge about APA, much of APA biological process is unknown and pending for further investigation. Herein, we review the current knowledge on APA and how its regulatory complex factors (CFI/IIm, CPSF, CSTF, and RBPs) work together to determine RNA splicing location, cell cycle velocity, microRNA processing, and oncogenesis regulation. We also discuss various APA experiment strategies and the future direction of APA research.

中文翻译：

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替代性聚腺苷酸化：转录后调控的新领域

信使前RNA（pre-mRNA）特异位点的聚腺苷酸化和其下游转录的终止由独特的序列基序结构（如AAUAAA及其辅助元件）发出信号。备选的聚腺苷酸化（APA）是一种重要的转录后调控机制，该机制取决于RNA产物的3'-非翻译区（3'-UTR）特异性序列信号。APA加工可从单个基因产生几种mRNA同工型，它们的靶基因可能具有不同的生物学功能。结果，细胞基因组稳定性，增殖能力和转化可行性都可能受到影响。此外，APA调节调节疾病的发生和发展。APA状态可能会成为疾病诊断，严重程度分层和预后预测的生物标志物。尽管现代整体技术（例如下一代测序（NGS）和单细胞测序技术）的进步丰富了我们对APA的了解，但APA的许多生物学过程尚不清楚，尚待进一步研究。本文中，我们回顾了有关APA的当前知识以及其调控复杂因子（CFI / IIm，CPSF，CSTF和RBP）如何共同作用，以确定RNA剪接位置，细胞周期速度，microRNA加工和肿瘤发生调控。我们还将讨论各种APA实验策略以及APA研究的未来方向。我们回顾了有关APA的当前知识及其调节复杂因子（CFI / IIm，CPSF，CSTF和RBP）如何共同确定RNA剪接位置，细胞周期速度，microRNA加工和致癌性调节。我们还将讨论各种APA实验策略以及APA研究的未来方向。我们回顾了有关APA的当前知识及其调节复杂因子（CFI / IIm，CPSF，CSTF和RBP）如何共同确定RNA剪接位置，细胞周期速度，microRNA加工和致癌性调节。我们还将讨论各种APA实验策略以及APA研究的未来方向。