新生 mRNA 的替代加工在真核生物中广泛存在，并且极大地影响基因表达的输出。具体来说，选择性切割和多腺苷酸化 (APA) 是一种共转录分子过程，可切换新生 mRNA 切割的多腺苷酸化位点 (PAS)，从而产生具有不同 3'UTR 长度和内容的 mRNA 亚型。 APA 可能会影响 mRNA 翻译效率、定位、稳定性和 mRNA 种子蛋白-蛋白相互作用。 APA 在发育和细胞分化过程中自然发生，大约 70% 的人类基因在特定组织和细胞类型中表现出 APA。例如，由于在比其他细胞类型中使用的其他 PAS 更远端的 PAS 上优先进行加工，神经元倾向于表达具有长 3'UTR 的 mRNA。此外，APA的变化标志着多种病理状态，包括许多类型的癌症，其中mRNA优先在更近端的PAS处裂解，导致具有短3'UTR的mRNA亚型的表达。尽管 APA 已被广泛报道，但 APA 在发育中的功能以及在正常和致病条件下调节 3' 末端切割位点选择的机制仍然知之甚少。在这篇综述中，我们总结了目前对 APA 在发育和细胞分化过程中如何调节以及由此产生的 3'UTR 含量变化如何影响基因表达的多个方面的理解。随着 APA 成为一种普遍现象、尖端科学技术的出现以及体内研究的迫切需要，现在是深入研究替代性裂解和多聚腺苷酸化的复杂机制的最佳时机。

Alternative processing of nascent mRNAs is widespread in eukaryotic organisms and greatly impacts the output of gene expression. Specifically, alternative cleavage and polyadenylation (APA) is a co-transcriptional molecular process that switches the polyadenylation site (PAS) at which a nascent mRNA is cleaved, resulting in mRNA isoforms with different 3'UTR length and content. APA can potentially affect mRNA translation efficiency, localization, stability, and mRNA seeded protein-protein interactions. APA naturally occurs during development and cellular differentiation, with around 70% of human genes displaying APA in particular tissues and cell types. For example, neurons tend to express mRNAs with long 3'UTRs due to preferential processing at PASs more distal than other PASs used in other cell types. In addition, changes in APA mark a variety of pathological states, including many types of cancer, in which mRNAs are preferentially cleaved at more proximal PASs, causing expression of mRNA isoforms with short 3'UTRs. Although APA has been widely reported, both the function of APA in development and the mechanisms that regulate the choice of 3'end cut sites in normal and pathogenic conditions are still poorly understood. In this review, we summarize current understanding of how APA is regulated during development and cellular differentiation and how the resulting change in 3'UTR content affects multiple aspects of gene expression. With APA being a widespread phenomenon, the advent of cutting-edge scientific techniques and the pressing need for in-vivo studies, there has never been a better time to delve into the intricate mechanisms of alternative cleavage and polyadenylation.