Impact of Dietary Interventions on Noncoding RNA Networks and mRNAs Encoding Chromatin-Related Factors

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Christopher D. Green, Yi Huang, Xiaoyang Dou, Liu Yang, Yong Liu, Jing-Dong J. Han
Dietary interventions dramatically affect metabolic disease and lifespan in various aging models. Here, we profiled liver microRNA (miRNA), coding, and long non-coding RNA (lncRNA) expression by high-throughput deep sequencing in mice across multiple energy intake and expenditure interventions. Strikingly, three dietary intervention network design patterns were uncovered: (1) lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; (2) protein-coding mRNAs with expression positively correlated with long lifespan are highly targeted by miRNAs; and (3) miRNA-targeting interactions mainly target chromatin-related functions. We experimentally validated miR-34a, miR-107, and miR-212-3p targeting of the chromatin remodeler Chd1 and further demonstrate that Chd1 knockdown mimics high-fat diet and aging-induced gene expression changes and activation of transposons. Our findings demonstrate lifespan-extending diets repress miRNA-chromatin remodeler interactions and safeguard against deregulated transcription induced by aging and lifespan shortening diets, events linked by microRNA, chromatin, and ncRNA crosstalk.

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Teaser

Through liver RNA sequencing and microRNA sequencing in mice across multiple energy intake and expenditure interventions, Green et al. found lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; miRNAs preferentially target mRNAs whose expression positively correlated with lifespan and modulate expression by targeting genes with chromatin-related functions.


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