A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification - Archive ouverte HAL Access content directly
Journal Articles Cardiovascular Research Year : 2022

A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification

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Isabelle Plaisance
  • Function : Author
Panagiotis Chouvardas
Yuliangzi Sun
  • Function : Author
Mohamed Nemir
  • Function : Author
Parisa Aghagolzadeh
  • Function : Author
Farhang Aminfar
  • Function : Author
Sophie Shen
  • Function : Author
Woo Jun Shim
  • Function : Author
Rory Johnson
  • Function : Author
Nathan Palpant
Thierry Pedrazzini

Abstract

Abstract 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 toward 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 functions 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.

Dates and versions

hal-03949322 , version 1 (20-01-2023)

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Isabelle Plaisance, Panagiotis Chouvardas, Yuliangzi Sun, Mohamed Nemir, Parisa Aghagolzadeh, et al.. A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification. Cardiovascular Research, 2022, ⟨10.1093/cvr/cvac191⟩. ⟨hal-03949322⟩

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