AKT-Dependent Phosphorylation of ADAR1p110 and ADAR2 Represents a New and Important Link Between Cell Signaling and RNA Editing

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Abstract

RNA editing is a process by which nascent RNA transcripts are covalently modified, thus enhancing the complexity of the transcriptome. The most common modifications are deaminations of adenosine to inosine at sites of complex RNA secondary structure, a process that is carried out by the adenosine deaminase acting on double-strand RNA (ADAR) family of RNA editases. Although much has been learned about the ADAR family members since their discovery, very little information on their post-transcriptional regulation has been reported. Similar to most proteins, the ADAR family members are post-translationally modified at multiple sites. We recently reported that members of the AKT kinase family directly phosphorylate ADAR1p110 and ADAR2 on a conserved threonine within the catalytic domain of the protein. Phosphorylation was observed to differentially inhibit the enzymatic activity of the ADAR proteins toward known RNA substrates. The direct downstream involvement of the AKT kinases in multiple major signaling pathways associated with cell survival, growth, glucose metabolism (insulin signaling), and differentiation is well established; thus, the AKT kinases represent a link between ADAR-dependent A-to-I editing and major signal transduction pathways that are necessary for cell maintenance and development.

Original languageEnglish
JournalDNA and Cell Biology
DOIs
Publication statusE-pub ahead of print - Jan 30 2020

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RNA Editing
Phosphorylation
RNA
Phosphotransferases
Inosine
Deamination
Proteins
Adenosine Deaminase
Threonine
Transcriptome
Adenosine
Signal Transduction
Catalytic Domain
Cell Survival
Maintenance
Insulin
Glucose
Growth

Cite this

@article{1e9ec67e5d694057b0bef12f6521f5e5,
title = "AKT-Dependent Phosphorylation of ADAR1p110 and ADAR2 Represents a New and Important Link Between Cell Signaling and RNA Editing",
abstract = "RNA editing is a process by which nascent RNA transcripts are covalently modified, thus enhancing the complexity of the transcriptome. The most common modifications are deaminations of adenosine to inosine at sites of complex RNA secondary structure, a process that is carried out by the adenosine deaminase acting on double-strand RNA (ADAR) family of RNA editases. Although much has been learned about the ADAR family members since their discovery, very little information on their post-transcriptional regulation has been reported. Similar to most proteins, the ADAR family members are post-translationally modified at multiple sites. We recently reported that members of the AKT kinase family directly phosphorylate ADAR1p110 and ADAR2 on a conserved threonine within the catalytic domain of the protein. Phosphorylation was observed to differentially inhibit the enzymatic activity of the ADAR proteins toward known RNA substrates. The direct downstream involvement of the AKT kinases in multiple major signaling pathways associated with cell survival, growth, glucose metabolism (insulin signaling), and differentiation is well established; thus, the AKT kinases represent a link between ADAR-dependent A-to-I editing and major signal transduction pathways that are necessary for cell maintenance and development.",
author = "Manuela Piazzi and Alberto Bavelloni and Angela Gallo and Blalock, {William L}",
year = "2020",
month = "1",
day = "30",
doi = "10.1089/dna.2020.5351",
language = "English",
journal = "DNA and Cell Biology",
issn = "1044-5498",
publisher = "Mary Ann Liebert Inc.",

}

TY - JOUR

T1 - AKT-Dependent Phosphorylation of ADAR1p110 and ADAR2 Represents a New and Important Link Between Cell Signaling and RNA Editing

AU - Piazzi, Manuela

AU - Bavelloni, Alberto

AU - Gallo, Angela

AU - Blalock, William L

PY - 2020/1/30

Y1 - 2020/1/30

N2 - RNA editing is a process by which nascent RNA transcripts are covalently modified, thus enhancing the complexity of the transcriptome. The most common modifications are deaminations of adenosine to inosine at sites of complex RNA secondary structure, a process that is carried out by the adenosine deaminase acting on double-strand RNA (ADAR) family of RNA editases. Although much has been learned about the ADAR family members since their discovery, very little information on their post-transcriptional regulation has been reported. Similar to most proteins, the ADAR family members are post-translationally modified at multiple sites. We recently reported that members of the AKT kinase family directly phosphorylate ADAR1p110 and ADAR2 on a conserved threonine within the catalytic domain of the protein. Phosphorylation was observed to differentially inhibit the enzymatic activity of the ADAR proteins toward known RNA substrates. The direct downstream involvement of the AKT kinases in multiple major signaling pathways associated with cell survival, growth, glucose metabolism (insulin signaling), and differentiation is well established; thus, the AKT kinases represent a link between ADAR-dependent A-to-I editing and major signal transduction pathways that are necessary for cell maintenance and development.

AB - RNA editing is a process by which nascent RNA transcripts are covalently modified, thus enhancing the complexity of the transcriptome. The most common modifications are deaminations of adenosine to inosine at sites of complex RNA secondary structure, a process that is carried out by the adenosine deaminase acting on double-strand RNA (ADAR) family of RNA editases. Although much has been learned about the ADAR family members since their discovery, very little information on their post-transcriptional regulation has been reported. Similar to most proteins, the ADAR family members are post-translationally modified at multiple sites. We recently reported that members of the AKT kinase family directly phosphorylate ADAR1p110 and ADAR2 on a conserved threonine within the catalytic domain of the protein. Phosphorylation was observed to differentially inhibit the enzymatic activity of the ADAR proteins toward known RNA substrates. The direct downstream involvement of the AKT kinases in multiple major signaling pathways associated with cell survival, growth, glucose metabolism (insulin signaling), and differentiation is well established; thus, the AKT kinases represent a link between ADAR-dependent A-to-I editing and major signal transduction pathways that are necessary for cell maintenance and development.

U2 - 10.1089/dna.2020.5351

DO - 10.1089/dna.2020.5351

M3 - Article

C2 - 31999481

JO - DNA and Cell Biology

JF - DNA and Cell Biology

SN - 1044-5498

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