Article

Yang, W. et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat. Struct. Mol. Biol. 13, 13-21

The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 02/2006; 13(1):13-21. DOI: 10.1038/nsmb1041
Source: PubMed

ABSTRACT

Adenosine deaminases acting on RNA (ADARs) are involved in editing of adenosine residues to inosine in double-stranded RNA (dsRNA). Although this editing recodes and alters functions of several mammalian genes, its most common targets are noncoding repeat sequences, indicating the involvement of this editing system in currently unknown functions other than recoding of protein sequences. Here we show that specific adenosine residues of certain microRNA (miRNA) precursors are edited by ADAR1 and ADAR2. Editing of pri-miR-142, the precursor of miRNA-142, expressed in hematopoietic tissues, resulted in suppression of its processing by Drosha. The edited pri-miR-142 was degraded by Tudor-SN, a component of RISC and also a ribonuclease specific to inosine-containing dsRNAs. Consequently, mature miRNA-142 expression levels increased substantially in ADAR1 null or ADAR2 null mice. Our results demonstrate a new function of RNA editing in the control of miRNA biogenesis.

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Available from: Kazuko Nishikura
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    • "In double-stranded regions of RNA, the I-U base pair is unstable compared to the parental A-U base pair, leading to changes in secondary structure of RNA that can result in degradation (Wang et al., 2013). In mammals, ADAR1 edits coding RNAs (Hartner et al., 2004), microRNAs (Yang et al., 2006), and the RNA transcripts of the prolific SINE retroelements (Osenberg et al., 2010). Interestingly, ADAR1 deficiency in mice results in embryonic lethality, accompanied by massive overproduction of type I IFNs and hematopoietic failure (Hartner et al., 2004, 2009; Wang et al., 2000). "
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    ABSTRACT: Mutations in ADAR, which encodes the ADAR1 RNA-editing enzyme, cause Aicardi-Goutières syndrome (AGS), a severe autoimmune disease associated with an aberrant type I interferon response. How ADAR1 prevents autoimmunity remains incompletely defined. Here, we demonstrate that ADAR1 is a specific and essential negative regulator of the MDA5-MAVS RNA sensing pathway. Moreover, we uncovered a MDA5-MAVS-independent function for ADAR1 in the development of multiple organs. We showed that the p150 isoform of ADAR1 uniquely regulated the MDA5 pathway, whereas both the p150 and p110 isoforms contributed to development. Abrupt deletion of ADAR1 in adult mice revealed that both of these functions were required throughout life. Our findings delineate genetically separable roles for both ADAR1 isoforms in vivo, with implications for the human diseases caused by ADAR mutations.
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    • "First, miRNAs that contain multiple inosines can themselves be targeted for degradation by specific ribonucleases (Garcia-Lopez et al., 2013). Editing sites in miRNA precursors can interfere with the efficiency of processing by Drosha (Yang et al., 2006b) or Dicer (Kawahara et al., 2007a), thus regulating the abundance of the mature miRNA. ADAR can also be beneficial to processing. "
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    ABSTRACT: All true metazoans modify their RNAs by converting specific adenosine residues to inosine. Because inosine binds to cytosine, it is a biological mimic for guanosine. This subtle change, termed RNA editing, can have diverse effects on various RNA-mediated cellular pathways, including RNA interference, innate immunity, retrotransposon defense and messenger RNA recoding. Because RNA editing can be regulated, it is an ideal tool for increasing genetic diversity, adaptation and environmental acclimation. This review will cover the following themes related to RNA editing: (1) how it is used to modify different cellular RNAs, (2) how frequently it is used by different organisms to recode mRNA, (3) how specific recoding events regulate protein function, (4) how it is used in adaptation and (5) emerging evidence that it can be used for acclimation. Organismal biologists with an interest in adaptation and acclimation, but with little knowledge of RNA editing, are the intended audience. © 2015. Published by The Company of Biologists Ltd.
    Full-text · Article · Jun 2015 · Journal of Experimental Biology
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    • "The purpose of these modifications is context dependent; for example, adenylation is required for selective stabilization of miR-122 in mouse liver (Katoh et al. 2009), whereas in THP-1 cell line, adenylation reduces effectiveness of miR-26a, miR- 27a, and miR-122 (Burroughs et al. 2010). In vitro editing of pri-mir-142 in two positions remarkably reduced pre-mir- 142 synthesis (Yang et al. 2006). This indicates that miRNA editing is one of the mechanisms that increase the repertoire of miRNAs and their targets. "
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    ABSTRACT: MicroRNAs (miRNAs) are transcriptional and posttranscriptional regulators involved in nearly all known biological processes in distant eukaryotic clades. Their discovery and functional characterization have broadened our understanding of biological regulatory mechanisms in animals and plants. They show both evolutionary conserved and unique features across Metazoa. Here, we present the current status of the knowledge about the role of miRNA in development, growth, and physiology of teleost fishes, in comparison to other vertebrates. Infraclass Teleostei is the most abundant group among vertebrate lineage. Fish are an important component of aquatic ecosystems and human life, being the prolific source of animal proteins worldwide and a vertebrate model for biomedical research. We review miRNA biogenesis, regulation, modifications, and mechanisms of action. Specific sections are devoted to the role of miRNA in teleost development, organogenesis, tissue differentiation, growth, regeneration, reproduction, endocrine system, and responses to environmental stimuli. Each section discusses gaps in the current knowledge and pinpoints the future directions of research on miRNA in teleosts.
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