衰老相关的细胞外囊泡小RNA货物。

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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引用次数: 0

摘要

先前对小鼠模型和人类的研究证明了rna的全局和组织特异性分子衰老轨迹。细胞外囊泡(EVs)是介导遗传信息在不同组织间水平传递的膜囊泡。我们在2-18个月的生命周期内的五个时间点对两个小鼠血浆组分中的小调控rna (sncRNAs)进行了测序:(1)自由循环的sncRNAs (fc-RNA)和(2)结合在ev外部或内部的sncRNAs (EV-RNA)。不同的sncRNA类别表现出独特的衰老模式,在fcRNA和EV-RNA部分之间有所不同。虽然trna在两个部分中都与衰老表现出最高的相关性,但rnas在EV-和fc-部分之间表现出负相关的轨迹。对于mirna, EV-RNA部分与衰老异常密切相关,尤其是脂肪组织中的miR-29家族。在一组27个月大的老年小鼠的独立队列中,对脂肪组织中的sncRNAs和编码基因进行测序,发现miR-29a-3p和miR-29b-3p在衰老相关基因调控中的关键作用,我们通过RT-qPCR在第三个队列中验证了这一点。
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Ageing-associated small RNA cargo of extracellular vesicles.

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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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
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
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