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Decoupling transcriptome layers: the distinct and variable nature of circular RNAs.

María Alonso-García1, Laurence Liaubet2, Thomas Faraut2

  • 1Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana, S/N, León, Spain.

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Summary

Circular RNAs (circRNAs) and messenger RNAs (mRNAs) exhibit distinct regulatory patterns. Analyzing both circRNAs and mRNAs in parallel reveals complementary gene regulation layers, crucial for understanding biological responses.

Keywords:
Circular transcriptomeExonic circRNAsExpressionLinear transcriptomeParental genes

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Area of Science:

  • Transcriptomics
  • Gene Regulation
  • Molecular Biology

Background:

  • Circular RNAs (circRNAs) and messenger RNAs (mRNAs) originate from the same genes but are produced via distinct splicing mechanisms.
  • This study investigates the comparative behavior of circular and linear transcriptomes across various biological conditions and tissues.

Purpose of the Study:

  • To analyze the distinct regulatory logics of circular and linear transcriptomes.
  • To understand their roles in response to infection and during tissue development and physiological variation.

Main Methods:

  • Analysis of transcriptomic data from bovine monocyte-derived macrophage (MDM) samples during Mycobacterium avium ssp. paratuberculosis (MAP) infection.
  • Examination of transcriptomic data from healthy bovine tissues (testes, liver, muscle) stratified by age, sex, and feed efficiency.

Main Results:

  • The circular transcriptome is approximately 100 times smaller than the linear transcriptome.
  • MAP infection primarily impacted the linear transcriptome in susceptible cattle (JD-), while circular transcriptomes showed less specific responses.
  • Tissue maturation and physiological factors like sex and feed efficiency induced distinct, often uncoordinated, changes in circular and linear transcriptomes.

Conclusions:

  • Circular and linear transcriptomes operate under largely independent regulatory mechanisms.
  • CircRNAs may exhibit higher variability and potentially carry fewer direct physiological signals compared to mRNAs, especially in the absence of clear linear transcriptome signatures.
  • Parallel analysis of both circRNAs and mRNAs is essential for a comprehensive understanding of gene regulation.