Genetic and genomic approaches to explore roles for the conserved 3'-5' exoribonuclease EXOSC10 in normal and malignant cells.

IF 4.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Pub Date : 2026-05-18 DOI:10.1261/rna.080981.126
Radhika Sain, Julian Primig, Michael Primig
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引用次数: 0

Abstract

EXOSC10 is a conserved 3'-5' exoribonuclease involved in processing ribosomal RNAs and degrading coding and noncoding transcripts as a catalytic subunit of the nuclear RNA exosome and in cooperation with cofactors. The protein is posttranslationally modified and shuttles between the nucleolus and the nucleus in response to oxygen deprivation in a process that involves sumoylation. EXOSC10 is of medical interest because its activity is inhibited by the anticancer drug 5-fluorouracil, which interferes with DNA replication and RNA-dependent processes. Moreover, high expression of EXOSC10 in certain somatic tumors is associated with patient survival. We discuss global and tissue-specific deletion experiments in the mouse, assess the protein's clinical relevance as a prognostic cancer biomarker in the context of human genomics data for normal versus malignant tissues, and explore EXOSC10's transcriptional regulatory network.

遗传学和基因组学方法探索保守的3‘-5’外核糖核酸酶EXOSC10在正常和恶性细胞中的作用。
EXOSC10是一种保守的3‘-5’外核糖核酸酶,作为核RNA外体的催化亚基,参与加工核糖体RNA,降解编码和非编码转录物,并与辅助因子合作。该蛋白在翻译后被修饰,并在一个涉及sumoylation的过程中响应缺氧在核仁和细胞核之间穿梭。EXOSC10具有医学意义,因为它的活性被抗癌药物5-氟尿嘧啶抑制,而5-氟尿嘧啶会干扰DNA复制和rna依赖过程。此外,EXOSC10在某些躯体肿瘤中的高表达与患者生存率相关。我们讨论了小鼠的全局和组织特异性缺失实验,评估了该蛋白在正常和恶性组织的人类基因组数据背景下作为预后癌症生物标志物的临床相关性,并探索了EXOSC10的转录调控网络。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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