Deciphering the Biological Significance of ADAR1–Z-RNA Interactions

Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme responsible for double-stranded RNA (dsRNA)-specific adenosine-to-inosine RNA editing, which is estimated to occur at over 100 million sites in humans. ADAR1 is composed of two isoforms transcribed from different promoters: p150 and N-terminal...

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Autores principales:	Taisuke Nakahama, Yukio Kawahara
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ADAR1 AGS IGS interferonopathy MDA5 RNA editing Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7b1d26b1b64f417ca659a23754e1fc4e
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spelling	oai:doaj.org-article:7b1d26b1b64f417ca659a23754e1fc4e2021-11-11T16:54:08ZDeciphering the Biological Significance of ADAR1–Z-RNA Interactions10.3390/ijms2221114351422-00671661-6596https://doaj.org/article/7b1d26b1b64f417ca659a23754e1fc4e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11435https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme responsible for double-stranded RNA (dsRNA)-specific adenosine-to-inosine RNA editing, which is estimated to occur at over 100 million sites in humans. ADAR1 is composed of two isoforms transcribed from different promoters: p150 and N-terminal truncated p110. Deletion of ADAR1 p150 in mice activates melanoma differentiation-associated protein 5 (MDA5)-sensing pathway, which recognizes endogenous unedited RNA as non-self. In contrast, we have recently demonstrated that ADAR1 p110-mediated RNA editing does not contribute to this function, implying that a unique Z-DNA/RNA-binding domain α (Zα) in the N terminus of ADAR1 p150 provides specific RNA editing, which is critical for preventing MDA5 activation. In addition, a mutation in the Zα domain is identified in patients with Aicardi–Goutières syndrome (AGS), an inherited encephalopathy characterized by overproduction of type I interferon. Accordingly, we and other groups have recently demonstrated that <i>Adar1</i> Zα-mutated mice show MDA5-dependent type I interferon responses. Furthermore, one such mutant mouse carrying a W197A point mutation in the Zα domain, which inhibits Z-RNA binding, manifests AGS-like encephalopathy. These findings collectively suggest that Z-RNA binding by ADAR1 p150 is essential for proper RNA editing at certain sites, preventing aberrant MDA5 activation.Taisuke NakahamaYukio KawaharaMDPI AGarticleADAR1AGSIGSinterferonopathyMDA5RNA editingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11435, p 11435 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ADAR1 AGS IGS interferonopathy MDA5 RNA editing Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ADAR1 AGS IGS interferonopathy MDA5 RNA editing Biology (General) QH301-705.5 Chemistry QD1-999 Taisuke Nakahama Yukio Kawahara Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
description	Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme responsible for double-stranded RNA (dsRNA)-specific adenosine-to-inosine RNA editing, which is estimated to occur at over 100 million sites in humans. ADAR1 is composed of two isoforms transcribed from different promoters: p150 and N-terminal truncated p110. Deletion of ADAR1 p150 in mice activates melanoma differentiation-associated protein 5 (MDA5)-sensing pathway, which recognizes endogenous unedited RNA as non-self. In contrast, we have recently demonstrated that ADAR1 p110-mediated RNA editing does not contribute to this function, implying that a unique Z-DNA/RNA-binding domain α (Zα) in the N terminus of ADAR1 p150 provides specific RNA editing, which is critical for preventing MDA5 activation. In addition, a mutation in the Zα domain is identified in patients with Aicardi–Goutières syndrome (AGS), an inherited encephalopathy characterized by overproduction of type I interferon. Accordingly, we and other groups have recently demonstrated that <i>Adar1</i> Zα-mutated mice show MDA5-dependent type I interferon responses. Furthermore, one such mutant mouse carrying a W197A point mutation in the Zα domain, which inhibits Z-RNA binding, manifests AGS-like encephalopathy. These findings collectively suggest that Z-RNA binding by ADAR1 p150 is essential for proper RNA editing at certain sites, preventing aberrant MDA5 activation.
format	article
author	Taisuke Nakahama Yukio Kawahara
author_facet	Taisuke Nakahama Yukio Kawahara
author_sort	Taisuke Nakahama
title	Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
title_short	Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
title_full	Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
title_fullStr	Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
title_full_unstemmed	Deciphering the Biological Significance of ADAR1–Z-RNA Interactions
title_sort	deciphering the biological significance of adar1–z-rna interactions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7b1d26b1b64f417ca659a23754e1fc4e
work_keys_str_mv	AT taisukenakahama decipheringthebiologicalsignificanceofadar1zrnainteractions AT yukiokawahara decipheringthebiologicalsignificanceofadar1zrnainteractions
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Deciphering the Biological Significance of ADAR1–Z-RNA Interactions

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