Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.
To systemically identify long noncoding RNAs (lncRNAs) regulating energy metabolism, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in key metabolic organs in mice under pathophysiologically representative metabolic conditions. Of 4,759 regulated lncRNAs, function-oriented filters yield 359 tissue-specifically regulated and metabolically sensitive lncRNAs that are predicted by lncRNA-mRNA correlation analyses to function in diverse aspects of energy metabolism. Specific regulations of liver metabolically sensitive lncRNAs (lncLMS) by nutrients, metabolic hormones, and key transcription factors were further defined in primary hepatocytes. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators. An lncLMS was experimentally confirmed in mice to suppress lipogenesis by forming a negative feedback loop in the SREBP1c pathway. Taken together, this study supports that a class of lncRNAs function as important metabolic regulators and establishes a framework for systemically investigating the role of lncRNAs in physiological homeostasis.
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ling
L
Yang
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ping
P
Li
Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Wenjing
W
Yang
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Xiangbo
X
Ruan
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kurtis
K
Kiesewetter
Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jun
J
Zhu
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: haiming.cao@nih.gov.
Haiming
H
Cao
D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
D006728:Hormones; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D014157:Transcription Factors
diabetes; energy metabolism; glucose; insulin; lincRNA; lipid; lncRNA; long non-coding RNA; metabolic disease; obesity
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