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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Adenosine to Inosine editing frequency controlled by splicing efficiency.

Konstantin Licht1, Utkarsh Kapoor1, Elisa Mayrhofer2

  • 1Department of Cell- and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria.

Nucleic Acids Research
|April 27, 2016
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Summary
This summary is machine-generated.

Splicing rates influence RNA editing levels when guided by intronic elements, but not exonic structures. Editing levels differ between pre- and mature mRNAs due to splicing and ADAR enzyme interactions.

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Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • Alternative splicing and adenosine to inosine (A to I) RNA editing are key co- and post-transcriptional RNA modifications.
  • Both processes occur in the nucleus, suggesting potential interplay.
  • Editing sites often rely on exon-intron basepairing, implying splicing could impact editing.

Purpose of the Study:

  • To investigate the influence of splicing rates on RNA editing levels.
  • To determine if this influence differs based on how editing sites are defined (intronic vs. exonic elements).
  • To explore discrepancies in editing levels between pre- and mature messenger RNAs (mRNAs).

Main Methods:

  • Systematic testing using reporter gene assays.
  • Analysis of endogenous RNA substrates.
  • Comparison of editing levels in pre-mRNA versus mature mRNA.

Main Results:

  • Splicing kinetics control RNA editing extent when editing is guided by intronic elements.
  • Editing sites defined solely by exonic structures are largely unaffected by adjacent intron splicing efficiency.
  • Editing levels in pre-mRNAs and mature mRNAs diverge, influenced by editing's effect on splicing and ADAR binding.

Conclusions:

  • Splicing efficiency is a regulatory factor for specific types of RNA editing.
  • The relationship between splicing and editing is context-dependent, based on the structural definition of editing sites.
  • Differential editing in pre- and mature RNAs is explained by reciprocal influences between editing, splicing, and ADAR binding.