Decoding the Long Noncoding RNA during Cardiac Maturation: a Roadmap for Functional Discovery [RNA]

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects (CHDs). Transcriptome programming during perinatal stages is important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated Overall design: From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45,167 unique transcripts were identified, including 21,916 known and 2,033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis (WGCNA) of mRNA and lncRNA datasets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while a few of them revealed chamber specific patterns. Out of 2,442 lncRNAs located within 50 KBs of protein coding genes, 11% significantly correlates with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. While this concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated CHD phenotypes RNA dataset: neonatal mouse heart left and right ventricles

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Touma M, Kang X, Zhao Y, Cass AA, Gao F, Biniwale R, Coppola G, Xiao X, Reemtsen B, Wang Y