Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Butler University, Indianapolis, Indiana, USA.
Wiley Interdiscip Rev RNA. 2023 May-Jun;14(3):e1757. doi: 10.1002/wrna.1757. Epub 2022 Aug 14.
The mammalian cleavage factor I subunit CFIm25 (NUDT21) binds to the UGUA sequences of precursor RNAs. Traditionally, CFIm25 is known to facilitate 3' end formation of pre-mRNAs resulting in the formation of polyadenylated transcripts. Recent studies suggest that CFIm25 may be involved in the cyclization and hence generation of circular RNAs (circRNAs) that contain UGUA motifs. These circRNAs act as competing endogenous RNAs (ceRNAs) that disrupt the ceRNA-miRNA-mRNA axis. Other emerging roles of CFIm25 include regulating both alternative splicing and alternative polyadenylation (APA). APA generates different sized transcripts that may code for different proteins, or more commonly transcripts that code for the same protein but differ in the length and sequence content of their 3' UTRs (3' UTR-APA). CFIm25 mediated global changes in 3' UTR-APA affect human physiology including spermatogenesis and the determination of cell fate. Deregulation of CFIm25 and changes in 3' UTR-APA have been implicated in several human diseases including cancer. In many cancers, CFIm25 acts as a tumor suppressor. However, there are some cancers where CFIm25 has the opposite effect. Alterations in CFIm25-driven 3' UTR-APA may also play a role in neural dysfunction and fibrosis. CFIm25 mediated 3' UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of CFIm25 as a regulator of the aforementioned RNA processing events, modulation of CFIm25 levels may be a novel viable therapeutic approach. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease.
哺乳动物剪接因子 I 亚基 CFIm25（NUDT21）与前体 RNA 的 UGUA 序列结合。传统上，CFIm25 被认为有助于前体 mRNA 的 3' 端形成，从而产生多聚腺苷酸化转录本。最近的研究表明，CFIm25 可能参与环化，从而产生含有 UGUA 基序的环状 RNA（circRNA）。这些 circRNA 作为竞争性内源性 RNA（ceRNA），破坏 ceRNA-miRNA-mRNA 轴。CFIm25 的其他新兴作用包括调节选择性剪接和选择性多聚腺苷酸化（APA）。APA 产生不同大小的转录本，可能编码不同的蛋白质，或者更常见的是编码相同蛋白质但 3'UTR 长度和序列内容不同的转录本（3'UTR-APA）。CFIm25 介导的 3'UTR-APA 的全局变化影响人类生理学，包括精子发生和细胞命运的决定。CFIm25 的失调和 3'UTR-APA 的变化与包括癌症在内的几种人类疾病有关。在许多癌症中，CFIm25 作为肿瘤抑制因子发挥作用。然而，在一些癌症中，CFIm25 则有相反的作用。CFIm25 驱动的 3'UTR-APA 的改变也可能在神经功能障碍和纤维化中发挥作用。CFIm25 介导的 3'UTR-APA 变化可用于生成特定的特征，可作为开发和疾病的潜在生物标志物。由于 CFIm25 作为上述 RNA 加工事件的调节因子的新兴作用，调节 CFIm25 水平可能是一种新的可行的治疗方法。本文归类于：RNA 加工>3' 端加工 RNA 在疾病和发育中的作用>RNA 在疾病中的作用。
