Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Jul;35(7):377-83.
doi: 10.1016/j.tibs.2010.02.008. Epub 2010 Apr 8.

ADAR editing in double-stranded UTRs and other noncoding RNA sequences

Heather A Hundley  1 , Brenda L Bass
Affiliations
Review

ADAR editing in double-stranded UTRs and other noncoding RNA sequences

Heather A Hundley et al. Trends Biochem Sci. 2010 Jul.

Abstract

ADARs are a family of enzymes, present in all animals, that convert adenosine to inosine within double-stranded RNA (dsRNA). Inosine and adenosine have different base-pairing properties, and thus, editing alters RNA structure, coding potential and splicing patterns. The first ADAR substrates identified were edited in codons, and ADARs were presumed to function primarily in proteome diversification. Although this is an important function of ADARs, especially in the nervous system, editing in coding sequences is rare compared to editing in noncoding sequences. Introns and untranslated regions of mRNA are the primary noncoding targets, but editing also occurs in small RNAs, such as miRNAs. Although the role of editing in noncoding sequences remains unclear, ongoing research suggests functions in the regulation of a variety of post-transcriptional processes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Endogenous RNAs edited by ADARs in non-coding sequences. The various types of endogenous RNA targeted by ADARs in base-paired, non-coding sequences are depicted in the subcellular compartment where they are observed (nucleus, purple oval; cytoplasm, beige oval). Colored rectangles show open-reading frames (ORF), with twin circles representing ribosomes translating an mRNA. In the cartoon, the exact sites of inosines (red stars) are not meaningful, but selective deamination is denoted by a single star in an RNA and non-selective deamination by multiple stars in an RNA. Small RNAs that are edited, including many pri-miRNAs and at least one pre- and one mature miRNA, have been identified in human cell lines [, –56, 58]. In addition, a large (~800 nucleotides), polyadenylated, non-coding RNA, rncs-1 (depicted with branched terminal structures), with multiple editing sites is present in C. elegans and antagonizes Dicer function [71]. Although some mammalian mRNAs with edited 3’ UTRs have been detected in the nucleus [32, 37], in both worms and human cell lines, mRNAs with edited 3’ UTRs are also present on translating ribosomes [31].
Figure 2
Figure 2
Models proposed to explain effects of ADARs on dsRNA-mediated gene silencing. miRNA (a) and siRNA (b) pathways are illustrated with precursors, intermediates and mature small RNAs represented as base-paired molecules. Middle pathways (shaded in light brown) show processing by Drosha (light blue oval) and/or Dicer (dark blue oval) in the absence of ADAR (green hexagon), and outer panels show effects of ADARs on processing (right) or re-targeting (left). Representative AU base-pairs are shown being converted to IU mismatches. (a) Drosha processes pri-miRNAs into ~70 nucleotide pre-miRNAs that are then processed into ~22 nucleotide miRNAs by Dicer; as shown, the mature miRNA strand then pairs with the target mRNA [53]. Editing events are detected at a variety of positions in pri-miRNAs, and inosines within both pri- and pre-miRNAs inhibit in vitro cleavage by Drosha and Dicer, respectively [42, 50]. In addition, inosine in at least one endogenous mature miRNA affects binding to mRNA targets [58]. (b) Transgenes that give rise to sense and antisense transcripts produce dsRNA that is edited by ADARs [62]. Inosines within such exogenous dsRNA, or within in vitro transcripts, inhibit processing by Dicer [61]. Although not yet experimentally validated, inosines within siRNAs are predicted to affect binding of siRNAs to target mRNAs. Editing has not been shown to affect the in vivo correlate of this pathway, the endo-siRNA pathway, and there are no reports of endo-siRNAs that contain inosine. However, the characteristics of ADARs make it likely to intersect with the endo-siRNA pathway.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gott JM, Emeson RB. Functions and mechanisms of RNA editing. Annu. Rev. Genet. 2000;34:499–531. - PubMed
    1. Bass BL. RNA editing by adenosine deaminases that act on RNA. Annu. Rev. Biochem. 2002;71:817–846. - PMC - PubMed
    1. Maydanovych O, Beal PA. Breaking the central dogma by RNA editing. Chem. Rev. 2006;106:3397–3411. - PubMed
    1. Nishikura K. Editor meets silencer: crosstalk between RNA editing and RNA interference. Nat. Rev. Mol. Cell. Biol. 2006;7:919–931. - PMC - PubMed
    1. Wang Q, et al. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science. 2000;290:1765–1768. - PubMed

Publication types

LinkOut - more resources