Regulation and function of alternative polyadenylation in development and differentiation.
Regulation and function of alternative polyadenylation in development and differentiation.
复制标题
DOI：
10.1080/15476286.2023.2275109
复制
发表时间：
2023-01
期刊：
影响因子：
4.1
通讯作者：
Fuller, Margaret T.
中科院分区：
文献类型：
--
作者：
Gallicchio, Lorenzo;Olivares, Gonzalo H.;Berry, Cameron W.;Fuller, Margaret T.
新生mrna的替代加工在真核生物中广泛存在，并极大地影响了基因表达的输出。具体来说，选择性裂解和聚腺苷化（APA）是一个共转录的分子过程，它改变了新生mRNA被裂解的聚腺苷化位点（PAS），导致mRNA亚型具有不同的3'UTR长度和内容。APA可能潜在地影响mRNA的翻译效率、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%的人类基因在特定的组织和细胞类型中显示APA。例如，神经元倾向于表达具有长3 ' utr的mrna，因为与其他细胞类型中使用的其他PASs相比，在更远的PASs处优先加工。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在更近端的PASs被优先切割，导致具有短3 ' utr的mRNA亚型的表达。尽管APA已被广泛报道，但在正常和致病条件下，APA在发育中的功能以及调节3 '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是如何调控的，以及由此导致的3'UTR含量的变化如何影响基因表达的多个方面的理解。随着APA的广泛存在，尖端科学技术的出现以及对体内研究的迫切需要，现在是深入研究选择性切割和聚腺苷酸化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.
登录
查看更多内容
在转录本的3'末端调节RNA加工因子的雄激素受体伴侣启动子募集。
影响因子：
14.9
作者：
Caggiano, Cinzia;Pieraccioli, Marco;Pitolli, Consuelo;Babini, Gabriele;Zheng, Dinghai;Tian, Bin;Bielli, Pamela;Sette, Claudio
通讯作者：
Sette, Claudio
影响因子：
56.9
作者：
de Morree, Antoine;Klein, Julian D. D.;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
β-无元素前mRNA的脑特异性启动子和聚腺苷酸位点产生异常长的3'-UTR。
影响因子：
14.9
作者：
Costessi, L;Devescovi, G;Baralle, FE;Muro, AF
通讯作者：
Muro, AF
影响因子：
8.8
作者：
Andreassi C;Luisier R;Crerar H;Darsinou M;Blokzijl-Franke S;Lenn T;Luscombe NM;Cuda G;Gaspari M;Saiardi A;Riccio A
通讯作者：
Riccio A
影响因子：
8.8
作者：
Chatrikhi, Rakesh;Mallory, Michael J.;Lynch, Kristen W.
通讯作者：
Lynch, Kristen W.