Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in...Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.展开更多
In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradat...In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.展开更多
转运RNA(transfer RNA,tRNA)可结合相应的氨基酸,并将其运送到核糖体上,促进蛋白质的翻译。tRNA衍生的小RNA(transfer RNA-derived small RNA,tsRNA)是tRNA被切割而产生的。tsRNA具有重要的生物学功能,可发挥调节基因表达和调控蛋白质...转运RNA(transfer RNA,tRNA)可结合相应的氨基酸,并将其运送到核糖体上,促进蛋白质的翻译。tRNA衍生的小RNA(transfer RNA-derived small RNA,tsRNA)是tRNA被切割而产生的。tsRNA具有重要的生物学功能,可发挥调节基因表达和调控蛋白质翻译等作用。近年来,研究揭示了tsRNA在癌症中的双重调控作用,特别是其在癌症患者体液中的显著差异性,强调了tsRNA作为一种潜在的肿瘤诊断和预后评估生物标志物的重要性。结直肠癌相关tsRNA中,5′tiRNA-His-GTG上调可促进肿瘤的发生和发展;由血管生成素切割产生的5′-tiRNA-Val上调,促进肿瘤转移和生长;tRF-20-MEJB5Y13上调,可促进结直肠癌细胞迁移和侵袭。胃癌相关tsRNA中,tRF-19-3L7L73JD上调可促进恶性肿瘤的进展,而tRF-24-V29K9UV3IU、tRF-5026a和tRF-Val上调可抑制肿瘤的增殖及进展。临床应用方面,血浆5-tRF-GlyGCC表达升高,诊断结直肠癌的曲线下面积达0.882,血浆tRF-5026a下降,诊断结直肠癌曲线下面积为0.883。胃癌患者血清tRF-27-FDXXE6XRK45、tRF-29-R9J8909NF5JP和tRF-23-Q99P9P9NDD的表达显著升高,诊断胃癌曲线下面积分别为0.805、0.889和0.783;三阴性乳腺癌血清中tDR-000620下降,与淋巴结转移和疾病复发相关。胃癌患者的血浆外泌体中,tRF-38、tRF-25和tRF-18表达升高,这些指标可用于诊断胃癌,且可能是术后预测因子;肝癌患者血浆外泌体的tRNA-ValTAC-3、tRNA-GlyTCC-5、tRNA-ValAAC-5和tRNA-GluCTC-5的表达水平明显增加,可能是新兴的标志物。本文综述了tsRNA的生成、分类及生物学功能,重点阐述tsRNA作为肿瘤标志物的研究进展以及其在不同肿瘤中发挥的作用。展开更多
基金supported by grants from the National Natural Science Foundation of China,Nos.81471238,81771327Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform,Budget of Beijing Municipal Health Commission 2020,No.PXM2020_026280_000002(all to BYL)。
文摘Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.
文摘In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.
文摘转运RNA(transfer RNA,tRNA)可结合相应的氨基酸,并将其运送到核糖体上,促进蛋白质的翻译。tRNA衍生的小RNA(transfer RNA-derived small RNA,tsRNA)是tRNA被切割而产生的。tsRNA具有重要的生物学功能,可发挥调节基因表达和调控蛋白质翻译等作用。近年来,研究揭示了tsRNA在癌症中的双重调控作用,特别是其在癌症患者体液中的显著差异性,强调了tsRNA作为一种潜在的肿瘤诊断和预后评估生物标志物的重要性。结直肠癌相关tsRNA中,5′tiRNA-His-GTG上调可促进肿瘤的发生和发展;由血管生成素切割产生的5′-tiRNA-Val上调,促进肿瘤转移和生长;tRF-20-MEJB5Y13上调,可促进结直肠癌细胞迁移和侵袭。胃癌相关tsRNA中,tRF-19-3L7L73JD上调可促进恶性肿瘤的进展,而tRF-24-V29K9UV3IU、tRF-5026a和tRF-Val上调可抑制肿瘤的增殖及进展。临床应用方面,血浆5-tRF-GlyGCC表达升高,诊断结直肠癌的曲线下面积达0.882,血浆tRF-5026a下降,诊断结直肠癌曲线下面积为0.883。胃癌患者血清tRF-27-FDXXE6XRK45、tRF-29-R9J8909NF5JP和tRF-23-Q99P9P9NDD的表达显著升高,诊断胃癌曲线下面积分别为0.805、0.889和0.783;三阴性乳腺癌血清中tDR-000620下降,与淋巴结转移和疾病复发相关。胃癌患者的血浆外泌体中,tRF-38、tRF-25和tRF-18表达升高,这些指标可用于诊断胃癌,且可能是术后预测因子;肝癌患者血浆外泌体的tRNA-ValTAC-3、tRNA-GlyTCC-5、tRNA-ValAAC-5和tRNA-GluCTC-5的表达水平明显增加,可能是新兴的标志物。本文综述了tsRNA的生成、分类及生物学功能,重点阐述tsRNA作为肿瘤标志物的研究进展以及其在不同肿瘤中发挥的作用。
