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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2022, Vol. 42 Issue (3): 82-90    DOI: 10.13523/j.cb.2108037
综述     
tsRNAs的作用机制及其在相关疾病中的潜在应用*
廖天赐,郑婷,沈林園,赵叶,牛丽莉,张顺华,朱砺**()
四川农业大学动物科技学院 四川农业大学畜禽遗传资源发掘与创新利用四川省重点实验室 成都 611130
Mechanisms of Action of tRNA-derived Small RNAs and Their Potential Roles in Related Diseases
LIAO Tian-ci,ZHENG Ting,SHEN Lin-yuan,ZHAO Ye,NIU Li-li,ZHANG Shun-hua,ZHU Li**()
College of Animal Science and Technology, Sichuan Agricultural University, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
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摘要:

近年来,转运RNA(transfer RNA,tRNA)衍生的小RNA(tRNA-derived small RNA,tsRNAs)被认为是一种新的、潜在的非编码RNAs(non-coding RNA,ncRNAs)。根据在前体或成熟tRNA上切割位置的不同,tsRNAs主要被分为两种类型,即tRNA halves(tRNA-derived stress-induced RNA,tiRNAs)和tRNA衍生片段(tRNA-derived fragment,tRFs)。越来越多的证据表明,tsRNAs参与翻译起始抑制、基因沉默和调节核糖体发生等多种细胞代谢过程,并在癌症、神经退行性疾病、代谢性疾病和病毒感染等相关疾病的发生、发展中都起着重要的作用。综述tsRNAs生物学功能和作用机制及其在相关疾病中的潜在应用,总结tsRNAs研究目前存在的问题和未来的研究方向。

关键词: tsRNAs非编码RNA转运RNARNA加工Small RNA    
Abstract:

Recently, tRNA-derived small RNAs (tsRNAs) were gradually recognized as a novel and potential non-coding RNAs (ncRNAs).There are mainly two types of tsRNAs, including tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence suggests that tsRNAs are implicated in various cellular processes, including translational inhibition, gene silencing, and ribosome biogenesis. They also play an important role in the development of related diseases such as cancer, neurodegeneration, metabolic diseases and viral infections. This review summarizes the functions and mechanisms of action of tsRNAs, the potential application of tsRNAs in related diseases,and the current problems and puts forward future research directions.

Key words: tsRNAs    ncRNAs    tRNA    RNA processing    Small RNA
收稿日期: 2021-08-12 出版日期: 2022-04-07
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(31972524);国家自然科学基金(31902135);四川省科技支撑计划资助项目(2021YFYZ0007);四川省科技支撑计划资助项目(2020YFN0147);四川省科技支撑计划资助项目(2021YJ0265)
通讯作者: 朱砺     E-mail: zhuli7508@163.com
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引用本文:

廖天赐, 郑婷, 沈林園, 赵叶, 牛丽莉, 张顺华, 朱砺. tsRNAs的作用机制及其在相关疾病中的潜在应用*[J]. 中国生物工程杂志, 2022, 42(3): 82-90.

LIAO Tian-ci, ZHENG Ting, SHEN Lin-yuan, ZHAO Ye, NIU Li-li, ZHANG Shun-hua, ZHU Li. Mechanisms of Action of tRNA-derived Small RNAs and Their Potential Roles in Related Diseases. China Biotechnology, 2022, 42(3): 82-90.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2108037        https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I3/82

图1  5种类型的tsRNAs图解
tsRNAs 类型 机制 生物学作用 参考文献
5' tiRNAAla 5' tiRNA 直接作用于elF4G,阻止翻译起始复合物的形成 抑制蛋白质翻译起始 [12-13]
5' tRF(Gln19) tRF-5 不需要互作的靶点,只需要5'-tRFs中普遍保守的“GG”二核苷酸 蛋白质翻译抑制 [14]
5' tRF(Lys19) tRF-5 不需要互作的靶点,只需要5'-tRFs中普遍保守的“GG”二核苷酸 蛋白质翻译抑制 [14]
CU1276 tRF-3 5'端的种子序列靶向RPA1的3' UTR,抑制RPA1的表达 抑制B细胞淋巴瘤细胞增殖 [15]
5'-tiRNA-His-GTG 5' tiRNA AGO1/3介导下,5'端种子序列靶向LATS2的3' UTR,抑制LATS2的表达 抑制凋亡,促进CRC细胞增殖 [16]
3'-tRFProTGG-19 tRF-3 5'端种子序列靶向Kcnma1的3' UTR,抑制Kcnma1的表达 造成血压紊乱 [17]
5'-tRF-GluCTC tRF-5 通过自身3'端与目标基因5'端结合,抑制细胞质靶mRNA 促进RSV的复制 [18]
3'-tsRNALeuCAG tRF-3 与核糖体蛋白RPS28 mRNAs结合,并增强其翻译 调控核糖体的生物发生 [19-20]
5'-tRFGlu tRF-5 与PIWIL4和PIWIL1形成复合物,促进CD1A启动子H3K9甲基化,抑制CD1A的表达 抑制免疫反应 [21]
5' tRFVal(CAC) tRF-5 与PIWIL4蛋白结合 抑制免疫反应 [22]
5' tRFGly(GCC) tRF-5 与PIWIL4蛋白结合 抑制免疫反应 [22]
3'-tRNA-Ala(UGC) tRF-3 3'端的CCACCA序列可以直接与Toll样受体(TLR)相互作用 激活Th1和毒性T淋巴细胞的免疫反应 [23]
5'-tiRNA-HisGUG 5' tiRNA 激活核内体TLR7 促进免疫反应 [24]
3'-tRNAGly-GCC tRF-3 直接切割mRNA部分互补的靶位部位 调节mRNA的稳定性 [15]
3'-tRNALeu-CAG tRF-3 直接切割mRNA部分互补的靶位部位 调节mRNA的稳定性 [25]
tRNAGluYTC tRF-2 与mRNA竞争性地结合YBX1 降低mRNA稳定性并促进降解 [26]
tRNAAspGTC tRF-2 与mRNA竞争性地结合YBX1 降低mRNA稳定性并促进降解 [26]
tiRNAArg-ACG 3' tiRNA 与线粒体释放的细胞色素C(Cyt C)相互作用,形成核糖核蛋白复合物 抑制凋亡体的形成和活性,抑制凋亡 [27]
表1  tsRNAs参与多种生物学功能
tsRNAs 类型 相关疾病 功能 参考文献
tRNAGluYTC
tRNAAspGTC
tRF-2 乳腺癌 与YBX1结合并破坏致癌转录本的稳定性来抑制乳腺癌 [26]
TDR-7816 tRF-2 乳腺癌 影响异种代谢过程促进乳腺癌发生 [38]
5' tiRNA-His-GTG 5' tiRNA 结直肠癌 靶向hippo信号通路,促进促增殖和抗凋亡相关基因的表达,加剧结直肠癌的发生 [16]
3'-tRF-ProTGG-19 tRF-3 高血压 抑制Kcnma1表达,加剧血压失调 [17]
tiRNA-Gly-GCC-002
TRF-Tyr-GTA-029
TRF-Thr-TGT-039
5' tiRNA
tRF-5
tRF-3
糖尿病性白内障 通过FoxO信号通路来调控DC发展 [39]
TRF-3001b tRF-3 非酒精性脂肪肝 靶向Prkaa1来抑制自噬,从而加重NAFLD的发展 [40]
3'-tRFlys3 tRF-3 HIV 和AGO2蛋白联合,通过RNAi机制靶向HIV [41]
5'-tRF-GluCTC tRF-5 RSV感染 靶向抑制ApoER2,从而促进RSV的复制 [18, 42]
3'-tRF-Tyr-GUA tRF-3 氧化应激 导致前体tRNA的显著耗尽,从而翻译抑制和生长抑制 [43]
tRF-20-MEJB5Y13 tRF-2 缺氧应激(CRC) 促使CRC细胞侵袭和迁移 [44]
tRF-315 tRF-3 顺铂重金属应激 保护前列腺癌细胞免受顺铂治疗诱导的线粒体依赖性细胞凋亡 [45]
表2  tsRNAs参与多种疾病
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