转运RNA衍生片段在衰老相关疾病中的研究进展

doi:10.3969/j.issn.1003-9198.2026.03.015

摘要/Abstract

摘要： 转运RNA衍生片段(transfer RNA-derived fragments, tRFs/tsRNAs)是由转运RNA(transfer RNA, tRNA)经特定核酸酶切割产生的非编码RNA,具有高度保守性、结构稳定性和功能多样性,其表达异常与多种疾病相关。tRFs的调控机制比微小RNA(microRNA, miRNA)更复杂,涉及类miRNA作用、调节翻译、结合蛋白等。随着人口老龄化,tRFs在肿瘤、神经退行性疾病及代谢综合征等衰老相关疾病中的表达失调受到关注。此外,tRFs在体液中的高稳定性使其成为潜在无创生物标志物。本综述总结了tRFs的分类及其在衰老相关疾病中的诊疗价值,旨在为该领域研究提供新视角。

关键词: 转运RNA衍生片段, 癌症, 阿尔茨海默病, 帕金森病, 生物标志物

Abstract: Transfer RNA-derived fragments (tRFs), generated through specific nuclease cleavage of transfer RNAs (tRNAs), represent a class of non-coding RNAs characterized by high evolutionary conservation, structural stability, and functional diversity. Their aberrant expression has been implicated in various pathological conditions, exhibiting regulatory mechanisms that are more intricate than those of microRNAs (miRNAs), which function through multiple pathways such as miRNA-like effect, translation regulating, and interactions with RNA-binding proteins. With the global trend of population aging, dysregulated expression of tRFs in aging-related pathologies, including neoplasms, neurodegenerative disorders, and metabolic syndromes, has garnered significant scientific attention. Furthermore, the remarkable stability of tRFs in bodily fluids makes them promising candidates for non-invasive biomarkers. This review summarizes the classification of tRFs and discusses their diagnostic and therapeutic potential in age-associated diseases, aiming to provide novel perspectives for advancing research in this emerging field.

Key words: transfer RNA-derived fragments, cancer, Alzheimer’s disease, Parkinson’s disease, biomarker

中图分类号:

R 393

德晓朦. 转运RNA衍生片段在衰老相关疾病中的研究进展[J]. 实用老年医学, 2026, 40(3): 299-303.

DE Xiaomeng. Advances of transfer RNA-derived fragments in age-related diseases[J]. Practical Geriatrics, 2026, 40(3): 299-303.

参考文献

[1] KUMAR P, MUDUNURI S B, ANAYA J, et al. tRFdb: a database for transfer RNA fragments[J]. Nucleic Acids Res, 2015, 43(Database issue): D141-D145.
[2] BOREK E, BALIGA B S, GEHRKE C W, et al. High turnover rate of transfer RNA in tumor tissue[J]. Cancer Res, 1977, 37(9): 3362-3366.
[3] LI J, ZHU L, CHENG J, et al. Transfer RNA-derived small RNA: a rising star in oncology[J]. Semin Cancer Biol, 2021, 75: 29-37.
[4] LI N, SHAN N, LU L, et al. tRFtarget: a database for transfer RNA-derived fragment targets[J]. Nucleic Acids Res, 2021, 49(D1): D254-D260.
[5] JIN F, YANG L, WANG W, et al. A novel class of tsRNA signatures as biomarkers for diagnosis and prognosis of pancreatic cancer[J]. Mol Cancer, 2021, 20(1): 95.
[6] YANG M, MO Y, REN D, et al. Transfer RNA-derived small RNAs in tumor microenvironment[J]. Mol Cancer, 2023, 22(1): 32.
[7] 巫杰, 柏玉, 沈瀚, 等. 血清转运RNA-LeuCAG-002与相关标志物对胰腺癌的诊断价值[J]. 标记免疫分析与临床, 2025, 32(1): 72-76.
[8] 骆雅鑫, 胡雪峰. 转运RNA衍生的小RNA研究概述[J]. 生物学教学, 2024, 49(1): 2-5.
[9] 李小晴, 朱传东, 陈芳芳. 转运RNA衍生的小RNA在乳腺癌中的作用及研究进展[J]. 中国医刊, 2023, 58(4): 374-378.
[10] WU W, SHEN A, LEE I, et al. Changes of tRNA-derived fragments by Alzheimer’s disease in cerebrospinal fluid and blood serum[J]. J Alzheimers Dis, 2023, 96(3): 1285-1304.
[11] XU J, QIAN B, WANG F, et al. Global profile of tRNA-derived small RNAs in pathological cardiac hypertrophy plasma and identification of tRF-21-NB8PLML3E as a new hypertrophy marker[J]. Diagnostics, 2023, 13(12): 2065.
[12] MAO M, CHEN W, HUANG X, et al. Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours[J]. Cell Commun Signal, 2023, 21(1): 178.
[13] CHEN Q, YAN M, CAO Z, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder[J]. Science, 2016, 351(6271): 397-400.
[14] KEAM S P, SOBALA A, TEN HAVE S, et al. tRNA-derived RNA fragments associate with human multisynthetase complex (MSC) and modulate ribosomal protein translation[J]. J Proteome Res, 2017, 16(2): 413-420.
[15] MADRER N, VAKNINE-TREIDEL S, ZORBAZ T, et al. Pre-symptomatic Parkinson’s disease blood test quantifying repetitive sequence motifs in transfer RNA fragments[J]. Nat Aging, 2025, 5(5): 868-882.
[16] PALDOR I, MADRER N, VAKNINE TREIDEL S, et al. Cerebrospinal fluid and blood profiles of transfer RNA fragments show age, sex, and Parkinson’s disease-related changes[J]. J Neurochem, 2023, 164(5): 671-683.
[17] DONG X, LI Q, LI R, et al. Inhibition of tRF- 02514 in extracellular vesicles preserves microglia pyroptosis and protects against Parkinson’s disease[J]. Mol Neurobiol, 2025, 62(9): 11047-11063.
[18] KUMAR P, ANAYA J, MUDUNURI S B, et al. Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets[J]. BMC Biol, 2014, 12: 78.
[19] THOMPSON D M, PARKER R. Stressing out over tRNA cleavage[J]. Cell, 2009, 138(2): 215-219.
[20] HONDA S, LOHER P, SHIGEMATSU M, et al. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers[J]. Proc Natl Acad Sci USA, 2015, 112(29): E3816-E3825.
[21] GOODARZI H, LIU X, NGUYEN H C B, et al. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement[J]. Cell, 2015, 161(4): 790-802.
[22] HAUSSECKER D, HUANG Y, LAU A, et al. Human tRNA-derived small RNAs in the global regulation of RNA silencing[J]. RNA, 2010, 16(4): 673-695.
[23] LOONEY M M, LU Y, KARAKOUSIS P C, et al. Mycobacterium tuberculosis infection drives mitochondria-biased dysregulation of host transfer RNA-derived fragments[J]. J Infect Dis, 2021, 223(10): 1796-1805.
[24] WANG Q, SONG X, ZHANG Y, et al. A pro-metastatic tRNA fragment drives aldolase A oligomerization to enhance aerobic glycolysis in lung adenocarcinoma[J]. Cell Rep, 2024, 43(8): 114550.
[25] 马剑峰, 甘麦邻, 朱砺, 等. 转运RNA衍生的小RNA功能及其研究方法[J]. 遗传, 2021, 43(12): 1107-1120.
[26] 苏玉, 秦榕, 章羽露, 等. 转运RNA衍生的小RNA在消化系统疾病中的研究进展[J]. 临床内科杂志, 2024, 41(6): 433-434.
[27] MO D, JIANG P, YANG Y, et al. A tRNA fragment, 5′-tiRNA^Val, suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer[J]. Cancer Lett, 2019, 457: 60-73.
[28] BLANCO S, BANDIERA R, POPIS M, et al. Stem cell function and stress response are controlled by protein synthesis[J]. Nature, 2016, 534(7607): 335-340.
[29] KIM H K, FUCHS G, WANG S, et al. A transfer-RNA-derived small RNA regulates ribosome biogenesis[J]. Nature, 2017, 552(7683): 57-62.
[30] LIU X, MEI W, PADMANABAN V, et al. A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of its bound metabolic mRNAs[J]. Mol Cell, 2022, 82(14): 2604-2617.e8.
[31] SCHELTENS P, DE STROOPER B, KIVIPELTO M, et al. Alzheimer’s disease [J]. Lancet, 2021, 397(10284): 1577-1590.
[32] ZHANG S, LI H, ZHENG L, et al. Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain[J]. Aging, 2019, 11(22): 10485-10498.
[33] WU W, LEE I, SPRATT H, et al. tRNA-derived fragments in Alzheimer’s disease: implications for new disease biomarkers and neuropathological mechanisms[J]. J Alzheimers Dis, 2021, 79(2): 793-806.
[34] ZHANG X, TREBAK F, SOUZA L A C, et al. Small RNA modifications in Alzheimer’s disease[J]. Neurobiol Dis, 2020, 145: 105058.
[35] DUBNOV S, BENNETT E R, YAYON N, et al. Knockout of the longevity gene Klotho perturbs aging and Alzheimer’s disease-linked brain microRNAs and tRNA fragments[J]. Commun Biol, 2024, 7(1): 720.
[36] PICKRELL A M, YOULE R J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease[J]. Neuron, 2015, 85(2): 257-273.
[37] PREHN J H M, JIRSTRÖM E. Angiogenin and tRNA fragments in Parkinson’s disease and neurodegeneration[J]. Acta Pharmacol Sin, 2020, 41: 442-446.
[38] 唐明敏, 毕洪运, 董子敬, 等. 转运RNA的表观遗传修饰及其异常对神经退行性变性疾病的影响[J]. 浙江大学学报(医学版), 2025, 54(1): 58-69.
[39] MATHEW B A, KATTA M, LUDHIADCH A, et al. Role of tRNA-derived fragments in neurological disorders: a review[J]. Mol Neurobiol, 2023, 60(2): 655-671.
[40] TIAN H, HU Z, WANG C. The therapeutic potential of tRNA-derived small RNAs in neurodegenerative disorders[J]. Aging Dis, 2022, 13(2): 389-401.
[41] FURMAN B L. Streptozotocin-induced diabetic models in mice and rats[J]. Curr Protoc, 2021, 1(4): e78.
[42] HAN X, CAI L, LU Y, et al. Identification of tRNA-derived fragments and their potential roles in diabetic cataract rats[J]. Epigenomics, 2020, 12(16): 1405-1418.
[43] ZHANG Y, CAI F, LIU J, et al. Transfer RNA-derived fragments as potential exosome tRNA-derived fragment biomarkers for osteoporosis[J]. Int J Rheum Dis, 2018, 21(9): 1659-1669.