转运RNA衍生的小RNA功能及其研究方法

doi:10.16288/j.yczz.21-256

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Hereditas(Beijing) ›› 2021, Vol. 43 ›› Issue (12): 1107-1120.doi: 10.16288/j.yczz.21-256

• Review • Previous Articles Next Articles

The function and research methods of tRNA-derived small RNAs (tsRNA)

Jianfeng Ma^1,²(), Mailin Gan^1,², Li Zhu^1,²(), Linyuan Shen^1,²()

1. College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China
2. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China

Received:2021-07-16 Revised:2021-09-17 Online:2021-12-20 Published:2021-11-23
Contact: Zhu Li,Shen Linyuan E-mail:1098991954@qq.com;zhuli7508@163.com;shenlinyuan0815@163.com
Supported by:
Supported by the National Natural Science Foundation of China Nos(31902135);Supported by the National Natural Science Foundation of China Nos(31972524);the Sichuan Science and Technology Support Program Nos(2021YJ0265);the Sichuan Science and Technology Support Program Nos(2021YFYZ0007);the Sichuan Science and Technology Support Program Nos(2020YFN0147)

Abstract

Abstract:

tRNA-derived small RNA (tsRNA), a class of small non-coding RNAs processed from the precursor tRNA or mature tRNA, broadly exist in organisms and have features including high conservation, structural stability and tissue specificity. According to the different paths of biogenesis, tsRNA is classified into two major types, tRNA halves and tRNA-derived RNA fragments (tRFs). Many studies have revealed that the expression of tsRNA is significantly increased under a variety of cellular stress responses, and its involvement in the regulation of stress responses is conserved across different species. tsRNA plays an important role in various biological processes by regulating transcript stability, protein translation and epigenetic processes. Recent researches have shown that tsRNA has the potential as disease biomarkers and therapeutic targets, making it the focus of biomedical research. In this review, we summarize the research on tsRNA from aspects of biogenesis, function and research methods in order to provide a reference for relevant research.

Key words: non-coding RNA, tRNA-derived fragments, tsRNA, tRFs

Jianfeng Ma, Mailin Gan, Li Zhu, Linyuan Shen. The function and research methods of tRNA-derived small RNAs (tsRNA)[J]. Hereditas(Beijing), 2021, 43(12): 1107-1120.

Figures/Tables 5

Table 1

Fig. 1

Table 2

tsRNAs related to diseases"

疾病类型	tsRNA名称	表达情况	作用	参考文献
乳腺癌	ts-122	上调	促进正常乳腺上皮细胞增殖	[36]
	tRF^Glu、tRF^Asp、tRF^Gly、tRF^Tyr	下调	与YBX1结合,降低原癌基因mRNA稳定性	[20]
	tRF3E	下调	竞争性结合核仁素NCL,抑制p53表达	[37]
	5ʹ-tiRNA^Val	下调	抑制胃癌细胞FZD3/Wnt/β-Catenin通路	[38]
	tRF-17	下调	抑制THBS1介导的TGF-β1/SMAD3信号通路	[37]
胃癌	tRF-3019a	上调	靶向FBXO47调节胃癌细胞增殖、迁移侵袭	[39]
	tRF-3017A	上调	靶向肿瘤抑制基因NELL2,促进癌细胞迁移和侵袭	[40]
	tRF-19-3L7L73JD	下调	与肿瘤大小有关,抑制细胞增殖,诱导细胞凋亡	[41]
白血病	5ʹ-tRF^His	下调	不同类型的tsRNA表达失调	[42]
白血病	tRF-3019	上调	激活HTLV-1逆转录酶	[43]
前列腺癌	5ʹ-SHOT-RNA	上调	促进前列腺癌细胞的增殖	[44]
前列腺癌	tRF-315	上调	靶向肿瘤抑制基因 GADD45A,抑制顺铂治疗诱导的前列腺癌细胞凋亡	[45]
肺癌	tRF-Leu-CAG	上调	促进细胞增殖和细胞周期进程	[46]
肺癌	ts-46、ts-47	下调	抑制细胞集落的形成	[47]
结直肠癌	tRF-20-M0NK5Y93	下调	靶向Claudin-1,抑制细胞迁移和侵袭	[48]
	tRF/miR-1280	下调	通过Notch信号途径来抑制结肠直肠癌生长和转移	[49]
	5ʹ-tRF-GlyGCC	上调	结直肠癌组织中5ʹ-tRF-GlyGCC表达增加依赖于ALKBH3的上调	[50]
卵巢癌	tRF-03357	上调	靶向HMBOX1,促进卵巢癌细胞增殖,迁移和侵袭	[51]
卵巢癌	tRF5-Glu	下调	抑制卵巢癌细胞的增殖	[52]
膀胱癌	5ʹ-tRF-LysCTT	上调	其水平升高和早期疾病进展、治疗结果差显著相关	[53]
动脉粥样硬化	tRF-Gly-GCC	上调	调节内皮细胞和平滑肌细胞的细胞粘附、增殖、迁移	[54]
过敏性皮肤炎	tRF-28	下调	-	[55]
非酒精性脂肪肝	tRF-Val-CAC-005 tiRNA-His-GTG-001 tRF-Ala-CGC-006	上调	血浆中tsRNA 水平升高与肝纤维化程度呈正相关	[56]
呼吸合胞病毒感染	tRF5-GlnCTG	上调	tRF5-GlnCTG受核糖核酸酶 ELAC2 的调节,促进呼吸道合胞病毒复制	[57]
阿尔茨海默病	tRF5-GlyGCC tRF5-GluCTC tRF5-GlyCCC-2	上调	NSun2下调使 tRNA 甲基化程度降低,ANG介导的tRF产生增加	[58]
帕金森病	-	-	帕金森患者前额叶皮层、脑脊液和血清中鉴定出的tRFs可能成为生物标志物	[59]
烟雾病	-	-	中性粒细胞表达差异的tsRNA参与免疫反应、血管生成和代谢调节等过程	[60]
肌萎缩性脊髓侧索硬化症	5ʹValCAC	上调	血管生成素介导的应激反应增强,导致5ʹValCAC水平的增加	[61]

Table 2

Table 3

The database of tsRNA"

工具名称	特点	网址	时间
tRFdb	第一个tsRNA数据库,包括拟南芥、链球菌、黑腹果蝇、秀丽隐杆线虫、非洲爪蟾、斑马鱼、小鼠和人类8个物种	http://genome.bioch.virginia.edu/trfdb	2015
tDRmapper	提供tsRNA标准化命名方法和定量方案	https://github.com/sararselitsky/tDRmapper3	2015
tRF2Cancer	从sRNA深度测序数据中准确识别tRF,并评估它们在多种癌症中的表达,对tRF起源位点及其类型进行注释	http://rna.sysu.edu.cn/tRFfinder/	2016
SpermBase	专门用于多物种精子RNA的分析数据库,包括tsRNA	http://www.spermbase.org	2016
YM500v3	与癌症相关的小RNA测序数据集,包括tsRNA	http://ngs.ym.edu.tw/ym500/	2017
MINTmap	用于线粒体和核tsRNA定位,能对深度测序数据中的tsRNA进行识别和量化	https://github.com/TJU-CMC-Org/MINTmap/	2017
MINTbase v2.0	各种人体组织的核和线粒体tsRNA信息,以及前体tRNA的修饰信息	http://cm.jefferson.edu/MINTbase/	2018
PtRFdb	植物tsRNA数据库	http://www.nipgr.res.in/PtRFdb/	2018
tRex	第一个用于模式植物拟南芥tsRNA综合数据库	http://combio.pl/trex	2018
SPORTS1.0	可以基于RNA内的核苷酸错配预测潜在的RNA修饰位点	https://github.com/junchaoshi/sports1.0	2018
tRFexplorer	能够对TCGA数据库中tRNA片段进行差异表达分析	https://trfexplorer.cloud/	2019
DASHR 2.0	第一个整合人类小非编码RNA和RNA-seq成熟产物的数据库	https://lisanwanglab.org/DASHRv2	2019
BBCancer	包含15种癌症类型的5040种正常和肿瘤血液样本中的6种RNA的表达数据	http://bbcancer.renlab.org/	2020
OncotRF	癌症中tsRNA的鉴定和定量,异常表达的tsRNA和基因,以及相关性分析、生存分析和功能富集分析等	http://bioinformatics.zju.edu.cn/OncotRF	2020
tRFtarget	预测靶基因的结合位点、结合区域以及结合稳定性的自由能,以及相关实验证据	http://trftarget.net	2021
deepBase v3.0	整合多个癌症组织的数据,提供了最全面的非编码RNA表达图谱,构建了tsRNA、microRNA、snoRNA和lncRNA的生存图	http://rna.sysu.edu.cn/deepbase3/index.html	2021
tRFTar	基于CLIP-seq数据,提供tsRNA的靶标预测	http://www.rnanut.net/tRFTar/	2021
tRFTars	预测人类tsRNA靶标	http://trftars.cmuzhenninglab.org:3838/tar/	2021
tsRBase	该数据库收集了20个物种不同组织或细胞系的样本,包括tsRNA的表达模式和功能信息等详细内容	http://www.tsrbase.org	2021

Table 3

Table 4

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应激类型	样本类型	处理方式	tsRNA名称/类型	参考文献
氧化应激	HeLa细胞	H₂O₂处理	tsRNA-His(GTG)	[9]
	酵母(Saccharomyces)	H₂O₂处理	tsRNA-His(GTG)	[15]
	小鼠(Mus musculus)	亚砷酸盐	整体tsRNA水平上调	[16]
	胚胎成纤维细胞	亚砷酸盐	整体tsRNA水平上调	[16]
	U2OS细胞	亚砷酸盐	整体tsRNA水平上调	[17]
饥饿/营养缺乏	HepG2细胞	无血清培养液	Gly-tRNA halves、Val-tRNA halves等	[10]
	嗜热四膜虫(Tetrahymena thermophila)	氨基酸饥饿	整体tsRNA水平上调	[18]
	布氏锥虫(Trypanosoma brucei)	磷酸缓冲溶液孵育	3ʹ-tRNA^Thr half	[19]
缺氧	人乳腺癌细胞	-	tRF^Glu	[20]
缺氧	人乳腺癌细胞	5% O₂	tDR-0009、tDR-7336	[21]
高pH	嗜盐古生菌(Haloferax volcanii)	pH8.5~9.5	Val-tRF	[22]
热应激或冷应激	HepG2细胞	42℃或16℃	Val-tRNA halves	[10]
紫外或热应激	U2OS细胞	紫外照射或42℃	5ʹ -tiRNA^Met	[23]

全称	缩写	研究目的	相关文献
RNA下拉实验(RNA pulldown)	-	研究与目的RNA结合的蛋白质	Falconi等^[107]在乳腺癌细胞中筛选出与tRF3E结合的核仁素蛋白(nucleolin),揭示了tsRNA作为肿瘤抑制因子的分子机制;Akiyama等^[108]用血管生成素处理骨肉瘤细胞,利用RNA下拉从其中分离纯化5'-tiRNAGly-GCC
RNA免疫沉淀 (RNA immunoprecipitation)	RIP	研究与目的蛋白互作的RNA	利用RIP鉴定出与Argonaute2蛋白结合的tsRNA,如tRF-3003a^[39]、tRF-3019a^[105]
紫外交联与免疫共沉淀 (crosslinking immunoprecipitation)	CLIP	研究与目的蛋白互作的RNA	在人类乳腺癌细胞中进行了内源性YBX1的交联免疫共沉淀,随后进行了高通量测序(CLIP-seq),发现大量标记定位于tsRNA^[20]
光活性核苷增强的交联和免疫共沉淀(photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation)	PAR-CLIP	研究与目的蛋白互作的RNA	PAR-CLIP是以CLIP为基础改良的技术,Cho等^[109]用以证明tRF-U3-1与La/SSB之间的特异性相互作用;Kumar等^[64]首次对tRFs进行了Meta分析,PAR-CLIP数据显示,人HEK293细胞中5ʹ-tsRNA和3ʹ-tsRNA更倾向于与AGO1、3和4相关联,而不是与AGO2相关联
杂交的交联连接测序(cross-linking ligation and sequencing of hybrids)	CLASH	研究RNA与RNA的相互作用	AGO CLASH数据表明,tsRNA能与靶RNA互补序列相互作用,将其招募到AGO单重复合物中并调节其表达或功能^[35]

The function and research methods of tRNA-derived small RNAs (tsRNA)

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