How RNA editing keeps an I on physiology

Adenosine deaminases acting on RNAs convert adenosines (A) to inosines (I) in structured or double-stranded RNAs. In mammals, this process is widespread. In the human transcriptome, more than a million different sites have been identified that undergo an ADAR-mediated A-to-I exchange Inosines have a...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2022-11, Vol.323 (5), p.C1496-C1511
Main Authors: Goldeck, Marion, Gopal, Aiswarya, Jantsch, Michael F, Mansouri Khosravi, Hamid Reza, Rajendra, Vinod, Vesely, Cornelia
Format: Article
Language:English
Subjects:
Adenosine - genetics
Adenosine - metabolism
Animals
Antiviral Agents
Humans
Inosine - genetics
Inosine - metabolism
Mammals - genetics
Mammals - metabolism
RNA Editing - genetics
RNA, Double-Stranded
RNA, Viral
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
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Summary:Adenosine deaminases acting on RNAs convert adenosines (A) to inosines (I) in structured or double-stranded RNAs. In mammals, this process is widespread. In the human transcriptome, more than a million different sites have been identified that undergo an ADAR-mediated A-to-I exchange Inosines have an altered base pairing potential due to the missing amino group when compared to the original adenosine. Consequently, inosines prefer to base pair with cytosines but can also base pair with uracil or adenine. This altered base pairing potential not only affects protein decoding at the ribosome but also influences the folding of RNAs and the proteins that can associate with it. Consequently, an A to I exchange can also affect RNA processing and turnover (Nishikura K. 79: 321-349, 2010; Brümmer A, Yang Y, Chan TW, Xiao X. 8: 1255, 2017). All of these events will interfere with gene expression and therefore, can also affect cellular and organismic physiology. As double-stranded RNAs are a hallmark of viral pathogens RNA-editing not only affects RNA-processing, coding, and gene expression but also controls the antiviral response to double-stranded RNAs. Most interestingly, recent advances in our understanding of ADAR enzymes reveal multiple layers of regulation by which ADARs can control antiviral programs. In this review, we focus on the recoding of mRNAs where the altered translation products lead to physiological changes. We also address recent advances in our understanding of the multiple layers of antiviral responses and innate immune modulations mediated by ADAR1.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00191.2022