Abstract
Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as potential key regulators of heart development and related diseases, but their identities and functions remain elusive. In this study, we sought to identify and characterize the cardiac lincRNA transcriptome in the experimentally accessible zebrafish model by integrating bioinformatics analysis with experimental validation. By conducting genome-wide RNA sequencing profiling of zebrafish embryonic hearts, adult hearts, and adult muscle, we generated a high-confidence set of 813 cardiac lincRNA transcripts, 423 of which are novel. Among these lincRNAs, 564 are expressed in the embryonic heart, and 730 are expressed in the adult heart, including 2 novel lincRNAs, TCONS_00000891 and TCONS_00028686, which exhibit cardiac-enriched expression patterns in adult heart. Using a method similar to a fetal gene program, we identified 51 lincRNAs with differential expression patterns between embryonic and adult hearts, among which TCONS_00009015 responded to doxorubicin-induced cardiac stress. In summary, our genome-wide systematic identification and characterization of cardiac lincRNAs lays the foundation for future studies in this vertebrate model to elucidate crucial roles for cardiac lincRNAs during heart development and cardiac diseases.
Highlights
Cardiovascular development is a dynamic, spatiotemporally coordinated, and transcriptionally regulated process involving thousands of genes[1]
Our investigation of cardiac lincRNAs in a vertebrate developmental model revealed that these cardiac lincRNAs have crucial biological roles during heart development and may serve as potential key regulators in biological processes closely related to heart diseases
Based on a gene set analysis (GSA) between embryonic heart-enriched lincRNAs and functional gene sets associated with heart development and disease (Supplemental Table 4), the embryonic heart-enriched lincRNAs were significantly associated with mitogen-activated protein kinase (MAPK) signaling, heart function, heart contraction, and sarcomere organization (Fig. 5A)
Summary
Cardiovascular development is a dynamic, spatiotemporally coordinated, and transcriptionally regulated process involving thousands of genes[1]. Based on the phastCons scores, the conservation level of novel lincRNAs was similar to those of known lincRNAs in the Ensembl and zflncRNApedia databases[36], which are substantially lower than those of protein-coding transcripts (Fig. 2E).
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