RNA Editing by Adenosine Deaminases That Act on RNA

Abstract

ADARs are RNA editing enzymes that target double-stranded regions of nuclear-encoded RNA and viral RNA. These enzymes are particularly abundant in the nervous system, where they diversify the information encoded in the genome, for example, by altering codons in mRNAs. The functions of ADARs in known substrates suggest that the enzymes serve to fine-tune and optimize many biological pathways, in ways that we are only starting to imagine. ADARs are also interesting in regard to the remarkable double-stranded structures of their substrates and how enzyme specificity is achieved with little regard to sequence. This review summarizes ongoing investigations of the enzyme family and their substrates, focusing on biological function as well as biochemical mechanism.

Editor meets silencer: crosstalk between RNA editing and RNA interference

“…A→I editing of tRNAs, which is mediated by ADAT (adenosine deaminase acting on tRNA), occurs in eukaryotes and also in Escherichia coli 109 . ADAT1 edits A37 (near the anticodon) of tRNA Ala , and the heterodimeric ADAT2-ADAT3 complex edits A34 at the wobble position of the anticodon of a subset of tRNAs [3][4][5]110 . ADAR genes are thought to have evolved from ADAT genes [2][3][4][5]110 .…”

“…The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I) in double-stranded (ds)RNAs through the action of ADAR (adenosine deaminase acting on RNA) enzymes [3][4][5] . A→I RNA editing of a short dsRNA that has formed between a coding exon and nearby intron sequences can lead to a codon change and an alteration in the protein function.…”

“…RNA editing is a post-transcriptional-processing mechanism that results in an RNA sequence that is different from the one encoded by the genome, and thereby contributes to the diversity of gene products. There are different types of RNA-editing mechanism that either add or delete nucleotides, or that change one nucleotide into another 2 (BOX 1).The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I) in double-stranded (ds)RNAs through the action of ADAR (adenosine deaminase acting on RNA) enzymes [3][4][5] . A→I RNA editing of a short dsRNA that has formed between a coding exon and nearby intron sequences can lead to a codon change and an alteration in the protein function.…”

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

“…RNA editing by adenosine deaminases acting on RNA (ADARs) converts adenosines (A) to inosines (I) in structured and double-stranded regions of RNAs [1]. With respect to their basepairing properties, inosines resemble guanosines.…”

“…Their evolutionary conservation further underscores the importance of these editing events [4]. In mammals, ADAR1 and ADAR2 are the two active editing enzymes identified today [5]. While ADAR1 primarily edits non-coding regions and is required to mark endogenous RNAs as ‘self’ [6], ADAR2 seems more involved in editing coding regions of mRNAs [7].…”