Plaisance, Isabelle; Chouvardas, Panagiotis; Sun, Yuliangzi; Nemir, Mohamed; Aghagolzadeh, Parisa; Aminfar, Farhang; Shen, Sophie; Shim, Woo Jun; Rochais, Francesca; Johnson, Rory; Palpant, Nathan; Pedrazzini, Thierry (2023). A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification. Cardiovascular research, 119(6), pp. 1361-1376. Oxford University Press 10.1093/cvr/cvac191
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AIMS
The major cardiac cell types composing the adult heart arise from common multipotent precursor cells. Cardiac lineage decisions are guided by extrinsic and cell-autonomous factors, including recently discovered long noncoding RNAs (lncRNAs). The human lncRNA CARMEN, which is known to dictate specification towards the cardiomyocyte (CM) and the smooth muscle cell (SMC) fates, generates a diversity of alternatively spliced isoforms.
METHODS AND RESULTS
The CARMEN locus can be manipulated to direct human primary cardiac precursor cells (CPCs) into specific cardiovascular fates. Investigating CARMEN isoform usage in differentiating CPCs represents therefore a unique opportunity to uncover isoform-specific function in lncRNAs. Here, we identify one CARMEN isoform, CARMEN-201, to be crucial for SMC commitment. CARMEN-201 activity is encoded within an alternatively-spliced exon containing a MIRc short interspersed nuclear element. This element binds the transcriptional repressor REST (RE1 Silencing Transcription Factor), targets it to cardiogenic loci, including ISL1, IRX1, IRX5, and SFRP1, and thereby blocks the CM gene program. In turn, genes regulating SMC differentiation are induced.
CONCLUSIONS
These data show how a critical physiological switch is wired by alternative splicing and functional transposable elements in a long noncoding RNA. They further demonstrated the crucial importance of the lncRNA isoform CARMEN-201 in SMC specification during heart development.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Chouvardas, Panagiotis, Johnson, Rory Baldwin |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0008-6363 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
21 Dec 2022 10:20 |
Last Modified: |
14 Jun 2023 00:12 |
Publisher DOI: |
10.1093/cvr/cvac191 |
PubMed ID: |
36537036 |
Uncontrolled Keywords: |
Cardiac precursor cells Splicing Transposable elements long noncoding RNAs smooth muscle cells |
BORIS DOI: |
10.48350/176267 |
URI: |
https://boris.unibe.ch/id/eprint/176267 |
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