Impact of Dietary Interventions on Noncoding RNA Networks and mRNAs Encoding Chromatin-Related Factors.
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.
Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Christopher D
CD
Green
Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Yi
Y
Huang
Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Xiaoyang
X
Dou
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Liu
L
Yang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yong
Y
Liu
Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China. Electronic address: jdhan@picb.ac.cn.
Jing-Dong J
JJ
Han
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004032:Diet; D059305:Diet, High-Fat; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D008099:Liver / Q000502:physiology; D008136:Longevity / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
C489844:Chd1 protein, mouse; D002843:Chromatin; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
Chd1; calorie restriction; chromatin; exercise; high fat; lifespan; lncRNA; microRNA; transposon