A protein-protein interaction underlies the molecular basis for substrate recognition by an adenosine-to-inosine RNA-editing enzyme

Suba Rajendren, Aidan C. Manning, Haider Al-Awadi, Kentaro Yamada, Yuichiro Takagi, Heather Hundley

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine within double-stranded regions of RNA, resulting in increased transcriptomic diversity, as well as protection of cellular double-stranded RNA (dsRNA) from silencing and improper immune activation. The presence of dsRNA-binding domains (dsRBDs) in all ADARs suggests these domains are important for substrate recognition; however, the role of dsRBDs in vivo remains largely unknown. Herein, our studies indicate the Caenorhabditis elegans ADAR enzyme, ADR-2, has low affinity for dsRNA, but interacts with ADR-1, an editing-deficient member of the ADAR family, which has a 100-fold higher affinity for dsRNA. ADR-1 uses one dsRBD to physically interact with ADR-2 and a second dsRBD to bind to dsRNAs, thereby tethering ADR-2 to substrates. ADR-2 interacts with >1200 transcripts in vivo, and ADR-1 is required for 80% of these interactions. Our results identify a novel mode of substrate recognition for ADAR enzymes and indicate that protein-protein interactions can guide substrate recognition for RNA editors.

Original languageEnglish (US)
Pages (from-to)9647-9659
Number of pages13
JournalNucleic Acids Research
Volume46
Issue number18
DOIs
StatePublished - Oct 12 2018

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RNA Editing
Inosine
Adenosine Deaminase
Adenosine
Double-Stranded RNA
RNA
Enzymes
Proteins
Caenorhabditis elegans
RNA Interference
Double-Stranded RNA Binding Motif

ASJC Scopus subject areas

  • Genetics

Cite this

A protein-protein interaction underlies the molecular basis for substrate recognition by an adenosine-to-inosine RNA-editing enzyme. / Rajendren, Suba; Manning, Aidan C.; Al-Awadi, Haider; Yamada, Kentaro; Takagi, Yuichiro; Hundley, Heather.

In: Nucleic Acids Research, Vol. 46, No. 18, 12.10.2018, p. 9647-9659.

Research output: Contribution to journalArticle

Rajendren, Suba ; Manning, Aidan C. ; Al-Awadi, Haider ; Yamada, Kentaro ; Takagi, Yuichiro ; Hundley, Heather. / A protein-protein interaction underlies the molecular basis for substrate recognition by an adenosine-to-inosine RNA-editing enzyme. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 18. pp. 9647-9659.
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