Investigation of RNA editing sites within bound regions of RNA-binding proteins

Tyler Weirick, Giuseppe Militello, Mohammed Rabiul Hosen, David John, Joseph B. Moore, Shizuka Uchida*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

Studies in epitranscriptomics indicate that RNA is modified by a variety of enzymes. Among these RNA modifications, adenosine to inosine (A-to-I) RNA editing occurs frequently in the mammalian transcriptome. These RNA editing sites can be detected directly from RNA sequencing (RNA-seq) data by examining nucleotide changes from adenosine (A) to guanine (G), which substitutes for inosine (I). However, a careful investigation of such nucleotide changes must be conducted to distinguish sequencing errors and genomic mutations from the genuine editing sites. Building upon our recent introduction of an easy-to-use bioinformatics tool, RNA Editor, to detect RNA editing events from RNA-seq data, we examined the extent by which RNA editing events affect the binding of RNA-binding proteins (RBP). Through employing bioinformatic techniques, we uncovered that RNA editing sites occur frequently in RBP-bound regions. Moreover, the presence of RNA editing sites are more frequent when RNA editing islands were examined, which are regions in which RNA editing sites are present in clusters. When the binding of one RBP, human antigen R [HuR; encoded by ELAV-like protein 1 (ELAV1)], was quantified experimentally, its binding was reduced upon silencing of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) compared to the control—suggesting that the presence of RNA editing islands influence HuR binding to its target regions. These data indicate RNA editing as an important mediator of RBP–RNA interactions—a mechanism which likely constitutes an additional mode of post-transcription gene regulation in biological systems.

Original languageEnglish
Article number19
JournalHigh-Throughput
Volume8
Issue number4
ISSN2571-5135
DOIs
Publication statusPublished - Dec 2019
Externally publishedYes

Keywords

  • RNA
  • RNA editing
  • RNA-binding proteins
  • RNA-seq
  • Transcriptome

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