The Editor’s I on Disease Development

Adenosine-to-inosine (A-to-I) editing of RNA leads to deamination of adenosine to inosine. Inosine is interpreted as guanosine by the cellular machinery, thus altering the coding, folding, splicing, or transport of transcripts. A-to-I editing is tightly regulated. Altered editing has severe conseque...

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Bibliographic Details
Published in:Trends in genetics 2019-12, Vol.35 (12), p.903-913
Main Authors: Jain, Mamta, Jantsch, Michael F., Licht, Konstantin
Format: Article
Language:English
Subjects:
ADAR
Adenosine Deaminase - genetics
Animals
cancer
Disease Susceptibility - immunology
Drug Development
Gene Expression Regulation
Genetic Predisposition to Disease
Humans
Immunity - genetics
innate immunity
Isoenzymes
neurodegenerative disease
RNA Editing
RNA Processing, Post-Transcriptional
RNA therapeutics
RNA, Messenger - genetics
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Summary:Adenosine-to-inosine (A-to-I) editing of RNA leads to deamination of adenosine to inosine. Inosine is interpreted as guanosine by the cellular machinery, thus altering the coding, folding, splicing, or transport of transcripts. A-to-I editing is tightly regulated. Altered editing has severe consequences for human health and can cause interferonopathies, neurological disorders, and cardiovascular disease, as well as impacting on cancer progression. ADAR1-mediated RNA editing plays an important role in antiviral immunity and is essential for distinguishing between endogenous and viral RNA, thereby preventing autoimmune disorders. Interestingly, A-to-I editing can be used not only to correct genomic mutations at the RNA level but also to modulate tumor antigenicity with large therapeutic potential. We highlight recent developments in the field, focusing on cancer and other human diseases. Adenosine deaminase acting on RNA (ADAR)1 expression is largely correlated with tumor progression and has been identified as a new promising target for cancer immunotherapy.It has recently emerged that RNA editing plays a pivotal role in coronary heart disease.Double-stranded RNA sensors such as MDA5 provide innate immunity against several viral infections; however, dysregulation of RNA sensing can lead to autoimmune disorders.A-to-I RNA editing is tightly controlled and regulated at multiple levels.Site-directed RNA editing may develop into RNA therapeutics against human disease.
ISSN:0168-9525
DOI:10.1016/j.tig.2019.09.004