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A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
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Characterizing the interplay between gene nucleotide composition bias and splicing.

Sébastien Lemaire1, Nicolas Fontrodona1, Fabien Aubé1

  • 1Laboratory of Biology and Modelling of the Cell, Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, 46 Allée d'Italie Site Jacques Monod, F-69007, Lyon, France.

Genome Biology
|December 1, 2019
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Summary

Genome nucleotide composition bias influences exon recognition during splicing. Specific splicing factors bind GC-rich or AT-rich exons, linking genome organization to alternative splicing regulation.

Keywords:
Chromatin organizationGenomicNucleotide composition biasSplicing

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • Nucleotide composition bias significantly impacts human genome organization in 1D and 3D.
  • Investigating the relationship between nucleotide composition bias and alternative splicing regulation is crucial.

Purpose of the Study:

  • To explore the interplay between nucleotide composition bias and the regulation of exon recognition in splicing.
  • To identify specific splicing factors associated with GC-rich and AT-rich exons.

Main Methods:

  • Analysis of multiple RNA-sequencing datasets.
  • Identification and characterization of splicing factors.
  • Assessment of RNA secondary structures and binding sites.
  • Correlation analysis with chromatin organization and genomic domains.

Main Results:

  • Two distinct groups of splicing factors were identified, targeting approximately 3200 GC-rich and 4000 AT-rich exons.
  • GC-rich exons exhibit RNA secondary structures and depend on U1 snRNP proteins.
  • AT-rich exons feature decoy branch points and depend on U2 snRNP proteins.
  • Nucleotide composition bias affects local chromatin organization and exon recognition.

Conclusions:

  • Regional nucleotide bias leaves a footprint at the exon level, influencing splicing constraints.
  • Local chromatin organization and specific splicing factor recruitment alleviate these constraints.
  • Nucleotide composition bias directly links genome organization to alternative splicing.