The Epitranscriptome and Innate Immunity.

Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological princip...

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Main Authors: Mary A O'Connell, Niamh M Mannion, Liam P Keegan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-12-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005687&type=printable
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author Mary A O'Connell
Niamh M Mannion
Liam P Keegan
author_facet Mary A O'Connell
Niamh M Mannion
Liam P Keegan
author_sort Mary A O'Connell
collection DOAJ
description Our knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I) RNA editing by the adenine deaminase acting on RNA (ADAR) enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.
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spelling doaj-art-1874171979bd40c79a8d2e1d2de49ad12025-08-20T02:15:40ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-12-011112e100568710.1371/journal.pgen.1005687The Epitranscriptome and Innate Immunity.Mary A O'ConnellNiamh M MannionLiam P KeeganOur knowledge of the variety and abundances of RNA base modifications is rapidly increasing. Modified bases have critical roles in tRNAs, rRNAs, translation, splicing, RNA interference, and other RNA processes, and are now increasingly detected in all types of transcripts. Can new biological principles associated with this diversity of RNA modifications, particularly in mRNAs and long non-coding RNAs, be identified? This review will explore this question by focusing primarily on adenosine to inosine (A-to-I) RNA editing by the adenine deaminase acting on RNA (ADAR) enzymes that have been intensively studied for the past 20 years and have a wide range of effects. Over 100 million adenosine to inosine editing sites have been identified in the human transcriptome, mostly in embedded Alu sequences that form potentially innate immune-stimulating dsRNA hairpins in transcripts. Recent research has demonstrated that inosine in the epitranscriptome and ADAR1 protein establish innate immune tolerance for host dsRNA formed by endogenous sequences. Innate immune sensors that detect viral nucleic acids are among the readers of epitranscriptome RNA modifications, though this does preclude a wide range of other modification effects.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005687&type=printable
spellingShingle Mary A O'Connell
Niamh M Mannion
Liam P Keegan
The Epitranscriptome and Innate Immunity.
PLoS Genetics
title The Epitranscriptome and Innate Immunity.
title_full The Epitranscriptome and Innate Immunity.
title_fullStr The Epitranscriptome and Innate Immunity.
title_full_unstemmed The Epitranscriptome and Innate Immunity.
title_short The Epitranscriptome and Innate Immunity.
title_sort epitranscriptome and innate immunity
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005687&type=printable
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