尿苷酸化：一种重要的细胞内RNA监控方式

doi:10.16288/j.yczz.22-094

遗传 ›› 2022, Vol. 44 ›› Issue (6): 449-465.doi: 10.16288/j.yczz.22-094

尿苷酸化：一种重要的细胞内RNA监控方式

王娟(), 杨悦宁, 朴威兰, 金花()

北京理工大学生命学院分子医学与生物诊疗工信部重点实验室,北京 100081

收稿日期:2022-04-01 修回日期:2022-05-06 出版日期:2022-06-20 发布日期:2022-05-07
通讯作者: 金花 E-mail:15689312865@163.com;huajin@bit.edu.cn
作者简介:王娟,在读硕士研究生,专业方向：生物学/生物化学与分子生物学。E-mail: 15689312865@163.com
基金资助:
国家自然科学基金项目(31970622)

Uridylation: a vital way for cellular RNA surveillance

Juan Wang(), Yuening Yang, Weilan Piao, Hua Jin()

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China

Received:2022-04-01 Revised:2022-05-06 Online:2022-06-20 Published:2022-05-07
Contact: Jin Hua E-mail:15689312865@163.com;huajin@bit.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(31970622)

摘要/Abstract

摘要：

RNA尿苷酸化作为一种高效的转录后基因调控方式,几乎存在于所有的真核生物中。末端尿苷酸转移酶(terminal uridylyltransferase, TUTase)负责催化生物体内snRNA、miRNA、mRNA和其他ncRNA的单尿苷酸化(monouridylation)和寡尿苷酸化(oligouridylation)。研究表明,对非编码RNA中间产物的单尿苷酸化可以改变其最终产物和生成速度,而寡尿苷酸化常用于时空特异性降解特定RNA、清除质量异常的RNA和病毒RNA。尿苷酸化通过这两种方式调控RNA的生成和降解,进而影响生物的生殖和早期发育、细胞凋亡、肿瘤发生以及病毒感染等多个重要的生物过程。本文对尿苷酸化的现有研究成果进行综述,介绍了RNA 3′末端检测技术,重点阐述了尿苷酸化调控基因表达的分子机制和其在RNA监控以及多种生物过程中的关键性作用,最后讨论了待解决的科学问题和未来研究的重要方向,旨在为抗病毒和抗肿瘤的临床治疗提供新思路。

关键词: RNA修饰, 末端尿苷酸转移酶, 降解, RNA监控, 疾病

Abstract:

RNA uridylation is an efficient posttranscriptional regulator of gene expression conserved in almost all eukaryotes. Terminal uridylyltransferase (TUTase) are responsible for monouridylation and oligouridylation of various RNA substrates, including snRNA, miRNA, mRNA and other ncRNAs. Studies have demonstrated that monouridylation on ncRNA intermediates alters their ultimate products and processing rates, whereas oligouridylation is often employed to degrade particular RNAs with spatio-temporal specificity and responsible for clearance of the aberrant RNAs and viral RNAs. Uridylation regulates gene expression by these two ways, therefore affects several important biological processes including organismal reproduction and early development, apoptosis, tumorigenesis, as well as virus infection. In this review, we provide the summarization of current researches on uridylation, introduce several techniques widely used for RNA 3′ terminus detection, put more emphases on describing the mechanisms of how uridylation controls gene expression, and summarize the key roles of uridylation in RNA surveillance and several biological processes. Furthermore, we discuss other unsolved issues and crucial aspects of future research as well, with the aim of providing new ideas for anti-tumor and anti-virus therapies.

Key words: RNA modification, ternminal uridylyltransferase (TUTase), degradation, RNA surveillance, disease

王娟, 杨悦宁, 朴威兰, 金花. 尿苷酸化：一种重要的细胞内RNA监控方式[J]. 遗传, 2022, 44(6): 449-465.

Juan Wang, Yuening Yang, Weilan Piao, Hua Jin. Uridylation: a vital way for cellular RNA surveillance[J]. Hereditas(Beijing), 2022, 44(6): 449-465.

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蛋白家族及名称	种属	功能	靶标RNA
CID1	粟酒裂殖酵母	寡尿苷酸化	mRNA miRNA siRNA U6 snRNA
USIP-1	线虫	寡尿苷酸化	U6 snRNA
PUP-2	线虫	寡尿苷酸化	mRNA pre-miRNA siRNA
CDE-1	线虫	寡尿苷酸化	siRNA Viral RNA
Tailor	果蝇	单尿苷酸化寡尿苷酸化聚腺苷酸化	pre-miRNA 5S RNA snRNA snoRNA tRNA RNase MRP
Mkg-p (Monkey king protein)	果蝇	寡尿苷酸化	mRNA
TUT4 (TENT3A、PAPD3、ZCCHC11)	人类	寡尿苷酸化单尿苷酸化尿苷酸化	mRNA histone mRNA LINE-1 mRNA pre-miRNA miRNA Viral RNA Pre-rRNA Pol Ⅲ-ncRNA
TUT7 (TENT3B、PAPD6、ZCCHC6)	人类	寡尿苷酸化单尿苷酸化尿苷酸化	同TUT4靶标
TUT1 (Star-PAP、U6 TUTase、PAPD2)	人类	寡尿苷酸化聚腺苷酸化	U6 snRNA mRNA

尿苷酸化：一种重要的细胞内RNA监控方式

Uridylation: a vital way for cellular RNA surveillance

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