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Identification of Circular RNAs using RNA Sequencing
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ciRS-7 exonic sequence is embedded in a long non-coding RNA locus.

Steven P Barrett1, Kevin R Parker2, Caroline Horn1

  • 1Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States of America.

Plos Genetics
|December 14, 2017
PubMed
Summary
This summary is machine-generated.

Circular RNA ciRS-7 biogenesis is linked to the LINC00632 long non-coding RNA promoter. This study reveals ciRS-7 is spliced into linear transcripts, challenging previous assumptions about its unique origin.

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Area of Science:

  • Molecular Biology
  • Genomics
  • RNA Biology

Background:

  • Circular RNA ciRS-7 is highly studied but its biogenesis remains largely unknown.
  • A key question is the location of the ciRS-7 promoter.
  • Previous assumptions suggested ciRS-7 is exceptional due to a lack of sense linear RNA transcripts.

Purpose of the Study:

  • To investigate the biogenesis of circular RNA ciRS-7.
  • To identify the promoter region responsible for ciRS-7 transcription.
  • To develop a new model for the regulation of the ciRS-7 locus.

Main Methods:

  • Developed a novel algorithm to predict RNA promoters.
  • Utilized computational approaches and experimental validation (including RNA-seq and ChIP-seq).
  • Employed multiple orthogonal experimental assays to confirm predictions.

Main Results:

  • Predicted and validated that the human ciRS-7 promoter overlaps with the LINC00632 long non-coding RNA promoter.
  • Established that ciRS-7 exonic sequences are present in linear transcripts, flanked by cryptic exons in humans and mice.
  • Demonstrated that ciRS-7 biogenesis is regulated by the chromatin state of LINC00632 promoters.

Conclusions:

  • ciRS-7 biogenesis is similar to other circRNAs, being spliced into linear transcripts.
  • LINC00632 promoter chromatin state is the primary determinant of ciRS-7 expression.
  • The developed analytical framework enables genome-wide discovery of biological regulation missed in current annotations.