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年龄相关性白内障小鼠模型中转录 RNA 衍生片段的全基因组库。

Genome-Wide Repertoire of Transfer RNA-Derived Fragments in a Mouse Model of Age-Related Cataract.

机构信息

Eye Institute, Affiliated Hospital of Nantong University, Nantong, China.

Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Curr Eye Res. 2022 Oct;47(10):1397-1404. doi: 10.1080/02713683.2022.2110263. Epub 2022 Aug 23.

Abstract

PURPOSE

To investigate the roles of tRNA-derived small RNAs (tsRNAs) containing transfer RNA-derived fragments (tRFs) and tRNA halves in age-related cataracts (ARCs).

METHODS

Lens capsule tissue from Emory mice at 3 months and 8 months of age were dissected for integrated tsRNA and gene transcriptome sequencing. A quantitative real-time PCR assay (qRT-PCR) was performed for validating sequencing results. Bioinformatics analysis was constructed to reveal the roles of tsRNAs.

RESULTS

A total of 422 differential expression (DE) tsRNAs were changed, in which 156 were elevated while 266 were declined in 8-month-old mice. Subsequently, the gene sequencing data exhibited 375 upregulated and 456 downregulated DE genes. Validation by qRT-PCR in 5 selected upregulated tRFs was consistent with tsRNAs sequencing results. Moreover, bioinformatics analysis identified 25 downregulated target genes of the 5 validated tRFs. Furthermore, GO analysis revealed that these target genes were mainly enriched in camera-type eye development, sensory organ development, and so on.

CONCLUSION

Our study provides a novel perspective on the role of tsRNAs in the pathogenesis of ARC, and thus therapeutic potential targets for ARC.

摘要

目的

研究含有转移 RNA 衍生片段(tRFs)和 tRNA 片段的 tRNA 衍生小 RNA(tsRNAs)在年龄相关性白内障(ARC)中的作用。

方法

从 3 个月和 8 个月大的 Emory 小鼠的晶状体囊组织中进行整合 tsRNA 和基因转录组测序。进行定量实时 PCR 检测(qRT-PCR)以验证测序结果。构建生物信息学分析以揭示 tsRNAs 的作用。

结果

共检测到 422 个差异表达(DE)的 tsRNAs,其中 156 个在 8 个月大的小鼠中上调,266 个下调。随后,基因测序数据显示 375 个上调和 456 个下调的 DE 基因。对 5 个选定的上调 tRFs 进行 qRT-PCR 验证与 tsRNAs 测序结果一致。此外,生物信息学分析鉴定了这 5 个验证的 tRFs 的 25 个下调靶基因。此外,GO 分析表明这些靶基因主要富集在相机型眼发育、感觉器官发育等方面。

结论

本研究为 tsRNAs 在 ARC 发病机制中的作用提供了新的视角,因此为 ARC 提供了潜在的治疗靶点。

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