In vivo functional analysis of non-conserved human lncRNAs associated with cardiometabolic traits

Xiangbo Ruan, Ping Li, Yi Chen, Yu Shi, Mehdi Pirooznia, Fayaz Seifuddin, Hiroshi Suemizu, Yasuyuki Ohnishi, Nao Yoneda, Megumi Nishiwaki, James Shepherdson, Abhilash Suresh, Komudi Singh, Yonghe Ma, Cheng-fei Jiang and Haiming Cao ()
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Xiangbo Ruan: National Institutes of Health
Ping Li: National Institutes of Health
Yi Chen: National Institutes of Health
Yu Shi: National Institutes of Health
Mehdi Pirooznia: National Institutes of Health
Fayaz Seifuddin: National Institutes of Health
Hiroshi Suemizu: Central Institute for Experimental Animals
Yasuyuki Ohnishi: Central Institute for Experimental Animals
Nao Yoneda: Central Institute for Experimental Animals
Megumi Nishiwaki: Central Institute for Experimental Animals
James Shepherdson: National Institutes of Health
Abhilash Suresh: National Institutes of Health
Komudi Singh: National Institutes of Health
Yonghe Ma: National Institutes of Health
Cheng-fei Jiang: National Institutes of Health
Haiming Cao: National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) are considered non-conserved. Although lncRNAs have been shown to function in diverse pathophysiological processes in mice, it remains largely unknown whether human lncRNAs have such in vivo functions. Here, we describe an integrated pipeline to define the in vivo function of non-conserved human lncRNAs. We first identify lncRNAs with high function potential using multiple indicators derived from human genetic data related to cardiometabolic traits, then define lncRNA’s function and specific target genes by integrating its correlated biological pathways in humans and co-regulated genes in a humanized mouse model. Finally, we demonstrate that the in vivo function of human-specific lncRNAs can be successfully examined in the humanized mouse model, and experimentally validate the predicted function of an obesity-associated lncRNA, LINC01018, in regulating the expression of genes in fatty acid oxidation in humanized livers through its interaction with RNA-binding protein HuR.

Date: 2020
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DOI: 10.1038/s41467-019-13688-z

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