The emerging roles of CFIm25 (NUDT21/CPSF5) in human biology and disease.

IF 6.4 2区 生物学 Q1 CELL BIOLOGY Wiley Interdisciplinary Reviews: RNA Pub Date : 2023-05-01 Epub Date: 2022-08-14 DOI:10.1002/wrna.1757
Chioniso Patience Masamha
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Abstract

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.

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CFIm25(NUDT21/CPSF5)在人类生物学和疾病中的新作用。
哺乳动物裂解因子 I 亚基 CFIm25(NUDT21)与前体 RNA 的 UGUA 序列结合。传统上,CFIm25 被认为能促进前体 mRNA 的 3' 端形成,从而形成多聚腺苷酸转录本。最近的研究表明,CFIm25 可能参与了含有 UGUA 基序的环状 RNA(circRNA)的环化和生成。这些环状 RNA 可作为竞争性内源性 RNA(ceRNA),破坏 ceRNA-miRNA-mRNA 轴。CFIm25 的其他新作用包括调节替代剪接和替代多腺苷酸化(APA)。APA 生成不同大小的转录本,这些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其 3' UTR 的长度和序列内容不同的转录本(3' UTR-APA)。CFIm25 介导的 3' UTR-APA 全局变化会影响人类生理,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多种人类疾病有关。在许多癌症中,CFIm25 是一种肿瘤抑制因子。然而,在某些癌症中,CFIm25却具有相反的作用。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变化可用于生成特异性特征,这些特征可用作发育和疾病中的潜在生物标志物。由于CFIm25在上述RNA加工事件中扮演着新的调控角色,因此调节CFIm25的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。
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来源期刊
CiteScore
14.80
自引率
4.10%
发文量
67
审稿时长
6-12 weeks
期刊介绍: WIREs RNA aims to provide comprehensive, up-to-date, and coherent coverage of this interesting and growing field, providing a framework for both RNA experts and interdisciplinary researchers to not only gain perspective in areas of RNA biology, but to generate new insights and applications as well. Major topics to be covered are: RNA Structure and Dynamics; RNA Evolution and Genomics; RNA-Based Catalysis; RNA Interactions with Proteins and Other Molecules; Translation; RNA Processing; RNA Export/Localization; RNA Turnover and Surveillance; Regulatory RNAs/RNAi/Riboswitches; RNA in Disease and Development; and RNA Methods.
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