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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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The conserved long non-coding RNA CARMA regulates cardiomyocyte differentiation.

Maryam Kay1,2, Bahram M Soltani1, Mohamed Nemir2

  • 1Department of Molecular Genetics, Faculty of Biological Sciences Tarbiat Modares University, Tehran, Iran.

Cardiovascular Research
|August 30, 2021
PubMed
Summary

Researchers identified CARMA, a long non-coding RNA that regulates cardiomyocyte differentiation in human stem cells. CARMA interacts with microRNAs and the NOTCH pathway, revealing a new regulatory network for cardiac development.

Keywords:
Cardiomyocyte differentiationEmbryonic stem cellsLong non-coding RNAsNOTCHmiR-1-1miR-133a2

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Area of Science:

  • Stem cell biology
  • Molecular biology
  • Developmental biology

Background:

  • Pluripotent stem cell differentiation into cardiomyocytes requires precise regulation.
  • Long non-coding RNAs (lncRNAs) are crucial regulators of cell specification during development.

Purpose of the Study:

  • To identify lncRNAs involved in cardiogenesis during human embryonic stem cell (ESC) differentiation.
  • To elucidate the regulatory mechanisms controlling cardiomyocyte production.

Main Methods:

  • Integrated approach to identify lncRNAs in differentiating human ESCs.
  • Investigated the function of CARMA (CARdiomyocyte Maturation-Associated lncRNA) in cardiomyocyte differentiation.
  • Analyzed interactions between CARMA, microRNAs (MIR1-1, MIR133a2), and the NOTCH signaling pathway.

Main Results:

  • Identified CARMA, a conserved lncRNA that controls cardiomyocyte differentiation and maturation.
  • CARMA expression is inversely correlated with MIR1-1 and MIR133a2 expression, and CARMA knockdown enhances miRNA levels.
  • CARMA down-regulation affects MIR133a2 target genes, including RBPJ, a NOTCH pathway component. Upregulation of linc1230 and linc1335 improved cardiomyocyte production.

Conclusions:

  • A regulatory network involving CARMA, MIR1-1, MIR133a2, and the NOTCH pathway coordinates cardiogenesis in ESCs.
  • Identified three novel lncRNAs (CARMA, linc1230, linc1335) critical for cardiac differentiation.
  • These findings provide new insights into the molecular mechanisms governing stem cell-derived cardiomyocyte production.