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Identification of Widespread Ultra-Edited Human RNAs
Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity. It occurs when a genomically encoded adenosine (A) is converted to an inosine (I) by ADAR proteins. Sequencing reactions read inosine as guanosine (G); therefore,...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197674/ https://www.ncbi.nlm.nih.gov/pubmed/22028664 http://dx.doi.org/10.1371/journal.pgen.1002317 |
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author | Carmi, Shai Borukhov, Itamar Levanon, Erez Y. |
author_facet | Carmi, Shai Borukhov, Itamar Levanon, Erez Y. |
author_sort | Carmi, Shai |
collection | PubMed |
description | Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity. It occurs when a genomically encoded adenosine (A) is converted to an inosine (I) by ADAR proteins. Sequencing reactions read inosine as guanosine (G); therefore, current methods to detect A-to-I editing sites align RNA sequences to their corresponding DNA regions and identify A-to-G mismatches. However, such methods perform poorly on RNAs that underwent extensive editing (“ultra”-editing), as the large number of mismatches obscures the genomic origin of these RNAs. Therefore, only a few anecdotal ultra-edited RNAs have been discovered so far. Here we introduce and apply a novel computational method to identify ultra-edited RNAs. We detected 760 ESTs containing 15,646 editing sites (more than 20 sites per EST, on average), of which 13,668 are novel. Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements. Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base pairing with neighboring, inverted Alus creates particularly long double-stranded RNA structures. Ultra-editing sites are underrepresented in old Alu subfamilies, tend to be non-conserved, and avoid exons, suggesting that ultra-editing is usually deleterious. A possible biological function of ultra-editing could be mediated by non-canonical splicing and cleavage of the RNA near the editing sites. |
format | Online Article Text |
id | pubmed-3197674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31976742011-10-25 Identification of Widespread Ultra-Edited Human RNAs Carmi, Shai Borukhov, Itamar Levanon, Erez Y. PLoS Genet Research Article Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity. It occurs when a genomically encoded adenosine (A) is converted to an inosine (I) by ADAR proteins. Sequencing reactions read inosine as guanosine (G); therefore, current methods to detect A-to-I editing sites align RNA sequences to their corresponding DNA regions and identify A-to-G mismatches. However, such methods perform poorly on RNAs that underwent extensive editing (“ultra”-editing), as the large number of mismatches obscures the genomic origin of these RNAs. Therefore, only a few anecdotal ultra-edited RNAs have been discovered so far. Here we introduce and apply a novel computational method to identify ultra-edited RNAs. We detected 760 ESTs containing 15,646 editing sites (more than 20 sites per EST, on average), of which 13,668 are novel. Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements. Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base pairing with neighboring, inverted Alus creates particularly long double-stranded RNA structures. Ultra-editing sites are underrepresented in old Alu subfamilies, tend to be non-conserved, and avoid exons, suggesting that ultra-editing is usually deleterious. A possible biological function of ultra-editing could be mediated by non-canonical splicing and cleavage of the RNA near the editing sites. Public Library of Science 2011-10-20 /pmc/articles/PMC3197674/ /pubmed/22028664 http://dx.doi.org/10.1371/journal.pgen.1002317 Text en Carmi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Carmi, Shai Borukhov, Itamar Levanon, Erez Y. Identification of Widespread Ultra-Edited Human RNAs |
title | Identification of Widespread Ultra-Edited Human RNAs |
title_full | Identification of Widespread Ultra-Edited Human RNAs |
title_fullStr | Identification of Widespread Ultra-Edited Human RNAs |
title_full_unstemmed | Identification of Widespread Ultra-Edited Human RNAs |
title_short | Identification of Widespread Ultra-Edited Human RNAs |
title_sort | identification of widespread ultra-edited human rnas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197674/ https://www.ncbi.nlm.nih.gov/pubmed/22028664 http://dx.doi.org/10.1371/journal.pgen.1002317 |
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