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Repetitive elements regulate circular RNA biogenesis.

Jeremy E Wilusz1

  • 1Department of Biochemistry and Biophysics; Perelman School of Medicine; University of Pennsylvania ; Philadelphia, PA USA.

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|October 7, 2015
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Summary
This summary is machine-generated.

Intronic repetitive elements regulate splicing decisions, directing precursor mRNAs (pre-mRNAs) to form either linear mRNAs or highly abundant circular RNAs. This process, driven by complementary repeat base pairing, controls gene output and can lead to species-specific gene functions.

Keywords:
ADARAluLINE1backsplicingbase pairingcircRNAcircular RNAnoncoding RNApre-mRNA splicingretrotransposition

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Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • Eukaryotic precursor mRNAs (pre-mRNAs) were traditionally thought to splice into linear mRNAs for protein production.
  • Emerging evidence shows thousands of genes produce non-canonically spliced circular RNAs (circRNAs), often exceeding linear mRNA levels.

Purpose of the Study:

  • To investigate the regulatory mechanisms determining whether pre-mRNAs are spliced into linear mRNAs or circRNAs.
  • To elucidate the role of intronic repetitive elements in circRNA biogenesis.

Main Methods:

  • Analysis of pre-mRNA splicing pathways.
  • Identification and characterization of intronic repetitive elements and their role in backsplicing.
  • Comparative genomics to assess species-specific gene output.

Main Results:

  • Intronic repetitive elements, including transposon-derived sequences, are key regulators of linear mRNA versus circRNA production.
  • Complementary base pairing between sequences in two different introns initiates circRNA biogenesis by facilitating backsplicing.
  • Multiple intronic repeats allow for the production of distinct circRNAs from a single pre-mRNA, influencing gene output.

Conclusions:

  • Intronic repeats act as critical regulatory sequences controlling the choice between linear mRNA and circRNA formation.
  • This regulatory mechanism impacts gene function and can contribute to significant divergence in gene functions across species.