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Implications of polyadenylation in health and disease

机译：聚腺苷酸化对健康和疾病的影响

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Polyadenylation is the RNA processing step that completes the maturation of nearly all eukaryotic mRNAs. It is a two-step nuclear process that involves an endonucleolytic cleavage of the pre-mRNA at the 3′-end and the polymerization of a polyadenosine (polyA) tail, which is fundamental for mRNA stability, nuclear export and efficient translation during development. The core molecular machinery responsible for the definition of a polyA site includes several recognition, cleavage and polyadenylation factors that identify and act on a given polyA signal present in a pre-mRNA, usually an AAUAAA hexamer or similar sequence. This mechanism is tightly regulated by other cis -acting elements and trans -acting factors, and its misregulation can cause inefficient gene expression and may ultimately lead to disease. The majority of genes generate multiple mRNAs as a result of alternative polyadenylation in the 3′-untranslated region. The variable lengths of the 3′ untranslated regions created by alternative polyadenylation are a recognizable target for differential regulation and clearly affect the fate of the transcript, ultimately modulating the expression of the gene. Over the past few years, several studies have highlighted the importance of polyadenylation and alternative polyadenylation in gene expression and their impact in a variety of physiological conditions, as well as in several illnesses. Abnormalities in the 3′-end processing mechanisms thus represent a common feature among many oncological, immunological, neurological and hematological disorders, but slight imbalances can lead to the natural establishment of a specific cellular state. This review addresses the key steps of polyadenylation and alternative polyadenylation in different cellular conditions and diseases focusing on the molecular effectors that ensure a faultless pre-mRNA 3′ end formation.
机译：聚腺苷酸化是完成几乎所有真核mRNA成熟的RNA处理步骤。这是一个两步的核过程，涉及在3'端对pre-mRNA进行内切核酸酶解和聚腺苷（polyA）尾部的聚合，这对于mRNA的稳定性，核输出和发育过程中的有效翻译至关重要。负责polyA位点定义的核心分子机制包括几个识别，切割和聚腺苷酸化因子，它们识别并作用于存在于前mRNA（通常为AAUAAA六聚体或相似序列）中的给定polyA信号。该机制受到其他顺式作用元件和反式作用因子的严格调控，其失调会导致基因表达效率低下并最终导致疾病。由于3'非翻译区中的多聚腺苷酸化，大多数基因产生了多个mRNA。通过交替的聚腺苷酸化作用产生的3'非翻译区的可变长度是差异调节的可识别靶标，并且明显影响转录物的命运，最终调节基因的表达。在过去的几年中，几项研究强调了聚腺苷酸化和替代性聚腺苷酸化在基因表达中的重要性及其在多种生理状况以及几种疾病中的影响。因此，3'末端加工机制的异常代表了许多肿瘤学，免疫学，神经学和血液学疾病的共同特征，但是轻微的失衡会导致特定细胞状态的自然建立。这篇综述解决了在不同细胞条件和疾病中聚腺苷酸化和替代性聚腺苷酸化的关键步骤，重点是确保无缺陷的前mRNA 3'端形成的分子效应子。

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