Ageing-associated small RNA cargo of extracellular vesicles.

IF 3.6 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RNA Biology Pub Date : 2023-01-01 DOI:10.1080/15476286.2023.2234713

Fabian Kern, Thomas Kuhn, Nicole Ludwig, Martin Simon, Laura Gröger, Natalie Fabis, Ernesto Aparicio-Puerta, Abdulrahman Salhab, Tobias Fehlmann, Oliver Hahn, Annika Engel, Viktoria Wagner, Marcus Koch, Katarzyna Winek, Hermona Soreq, Irina Nazarenko, Gregor Fuhrmann, Tony Wyss-Coray, Eckart Meese, Verena Keller, Matthias W Laschke, Andreas Keller

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Abstract

Previous work on murine models and humans demonstrated global as well as tissue-specific molecular ageing trajectories of RNAs. Extracellular vesicles (EVs) are membrane vesicles mediating the horizontal transfer of genetic information between different tissues. We sequenced small regulatory RNAs (sncRNAs) in two mouse plasma fractions at five time points across the lifespan from 2-18 months: (1) sncRNAs that are free-circulating (fc-RNA) and (2) sncRNAs bound outside or inside EVs (EV-RNA). Different sncRNA classes exhibit unique ageing patterns that vary between the fcRNA and EV-RNA fractions. While tRNAs showed the highest correlation with ageing in both fractions, rRNAs exhibited inverse correlation trajectories between the EV- and fc-fractions. For miRNAs, the EV-RNA fraction was exceptionally strongly associated with ageing, especially the miR-29 family in adipose tissues. Sequencing of sncRNAs and coding genes in fat tissue of an independent cohort of aged mice up to 27 months highlighted the pivotal role of miR-29a-3p and miR-29b-3p in ageing-related gene regulation that we validated in a third cohort by RT-qPCR.

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细胞外囊泡中与衰老相关的小 RNA 货物。

以前在小鼠模型和人类身上进行的研究表明，RNA 的分子老化轨迹既有全球性的，也有组织特异性的。细胞外囊泡（EVs）是介导不同组织间遗传信息水平转移的膜囊泡。我们测序了小鼠血浆中两种小调控RNA（sncRNA）在2-18个月生命周期中五个时间点的情况：（1）自由循环的sncRNA（fc-RNA）和（2）结合在EV外部或内部的sncRNA（EV-RNA）。不同类别的 sncRNA 表现出独特的老化模式，这些模式在 fcRNA 和 EV-RNA 部分之间有所不同。tRNA 与两个部分的老化相关性最高，而 rRNA 则在 EV 和 fc 部分之间呈现出反相关轨迹。在 miRNAs 方面，EV-RNA 部分与衰老的相关性特别强，尤其是脂肪组织中的 miR-29 家族。我们通过 RT-qPCR 在第三个队列中验证了这一研究结果。

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来源期刊

RNA Biology 生物-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy