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衰老加速小鼠8号品系大脑中功能性tRNA衍生片段的鉴定

Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain.

作者信息

Zhang Shuai, Li Hejian, Zheng Ling, Li Hong, Feng Chengqiang, Zhang Wensheng

机构信息

Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Zhuhai, Guangdong 519087, China.

Engineering Research Center of Natural Medicine, Ministry of Education, Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China.

出版信息

Aging (Albany NY). 2019 Nov 20;11(22):10485-10498. doi: 10.18632/aging.102471.

Abstract

Transfer RNA-derived fragments (tRFs) are known to contribute to multiple illnesses, including cancers, viral infections, and age-related neurodegeneration. In this study, we used senescence-accelerated mouse prone 8 (SAMP8) as a model of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, and a control, the senescence-accelerated mouse resistant 1 (SAMR1) model, to comprehensively explore differences in tRF expression between them. We discovered 570 tRF transcripts among which eight were differentially expressed. We then obtained 110 potential target genes in a miRNA-like pattern. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation suggest that these target genes participate in a variety of brain functions; , synapse formation (GO: 0045202) and the synaptic vesicle cycle pathway. We further assessed in detail those tRFs whose miRNA-like pattern was most likely to promote the progression of either Alzheimer's or Parkinson's disease, such as AS-tDR-011775 acting on and . Our findings suggest the eight dysregulated tRFs we uncovered here may be beneficially exploited as potential diagnostic biomarkers and/or therapeutic targets to treat age-related brain diseases.

摘要

已知转运RNA衍生片段(tRFs)与多种疾病有关,包括癌症、病毒感染和与年龄相关的神经退行性疾病。在本研究中,我们使用衰老加速易患8型小鼠(SAMP8)作为阿尔茨海默病和帕金森病等神经退行性疾病的模型,并使用对照衰老加速抗性1型小鼠(SAMR1)模型,全面探索它们之间tRF表达的差异。我们发现了570个tRF转录本,其中8个差异表达。然后,我们以类似miRNA的模式获得了110个潜在靶基因。基因本体论(GO)和京都基因与基因组百科全书(KEGG)注释表明,这些靶基因参与多种脑功能;例如,突触形成(GO:0045202)和突触小泡循环途径。我们进一步详细评估了那些其类似miRNA模式最有可能促进阿尔茨海默病或帕金森病进展的tRFs,例如作用于……的AS-tDR-011775。我们的研究结果表明,我们在此发现的8个失调的tRFs可能作为潜在的诊断生物标志物和/或治疗靶点,用于治疗与年龄相关的脑部疾病,具有有益的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5647/6914438/cca8fb46559e/aging-11-102471-g001.jpg

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