A-to-I RNA Editing in Human Cells
type: CreativeWork
description: RNA editing is a means of diversifying the transcriptome and regulating innate immunity. Among the different classes of enzymes that modify RNA, adenosine deaminase acting on RNA (ADAR) is a type that catalyzes adenosine-to-inosine editing on double-stranded RNA molecules to regulate cellular responses to endogenous and exogenous RNA. Of the three ADAR homologs in humans, dysregulation of ADAR1 editing due to inherited mutations leads to disorders such as Aicardi-Goutieres syndrome, an inflammatory disease that manifests in the brain and skin, and dyschromatosis symmetrica hereditaria, a skin pigmentation disorder. ADAR1 is the primary A-to-I editor of RNA in humans, and the majority of edit sites are found in a class of repetitive elements called Alu, many of which are located in introns and 3' untranslated regions of RNA. The functional consequences of A-to-I editing are varied, although a complete lack of functional ADAR1 is usually not tolerated, as revealed by the MDA5-mediated embryonic lethality in mice lacking functional ADAR1. In human neural progenitor cells, loss of ADAR1 causes spontaneous upregulation of interferon and cell death, although the RNA triggers remain unknown. Given the importance of ADAR1-editing in maintaining homeostasis in various contexts, there is a need to understand in more detail how ADAR1 isoforms are regulated and how they individually contribute to the A-to-I RNA editome. Two ADAR1 protein isoforms, p110 (110 kDa) and p150 (150 kDa), are expressed constitutively and in response to interferon, respectively, but the contribution of each isoform to the editing landscape remains incompletely characterized, largely because of the challenges in expressing p150 without p110. We revealed that the p110 isoform can be expressed from the canonical p150-encoding mRNA due to leaky ribosome scanning downstream of the p150 start codon. Synonymous mutations introduced in the region between the p150 and p110 start codons reduce leaky scanning and…
abstract: RNA editing is a means of diversifying the transcriptome and regulating innate immunity. Among the different classes of enzymes that modify RNA, adenosine deaminase acting on RNA (ADAR) is a type that catalyzes adenosine-to-inosine editing on double-stranded RNA molecules to regulate cellular responses to endogenous and exogenous RNA. Of the three ADAR homologs in humans, dysregulation of ADAR1 editing due to inherited mutations leads to disorders such as Aicardi-Goutieres syndrome, an inflammatory disease that manifests in the brain and skin, and dyschromatosis symmetrica hereditaria, a skin pigmentation disorder. ADAR1 is the primary A-to-I editor of RNA in humans, and the majority of edit sites are found in a class of repetitive elements called Alu, many of which are located in introns and 3' untranslated regions of RNA. The functional consequences of A-to-I editing are varied, although a complete lack of functional ADAR1 is usually not tolerated, as revealed by the MDA5-mediated embryonic lethality in mice lacking functional ADAR1. In human neural progenitor cells, loss of ADAR1 causes spontaneous upregulation of interferon and cell death, although the RNA triggers remain unknown. Given the importance of ADAR1-editing in maintaining homeostasis in various contexts, there is a need to understand in more detail how ADAR1 isoforms are regulated and how they individually contribute to the A-to-I RNA editome. Two ADAR1 protein isoforms, p110 (110 kDa) and p150 (150 kDa), are expressed constitutively and in response to interferon, respectively, but the contribution of each isoform to the editing landscape remains incompletely characterized, largely because of the challenges in expressing p150 without p110. We revealed that the p110 isoform can be expressed from the canonical p150-encoding mRNA due to leaky ribosome scanning downstream of the p150 start codon. Synonymous mutations introduced in the region between the p150 and p110 start codons reduce leaky scanning and…
author: Sun, Tony
keywords: ADAR, RNA editing, isoforms, innate immunity, leaky scanning, A-to-I editing, Life Sciences
date published: 2021-01-01T08:00:00Z
date modified: 2026-07-24T04:11:45Z
provider: Rockefeller
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rockefeller