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Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing

Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HD...

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Autores principales: Hsu, Chao-Wei, Juang, Horng-Heng, Kuo, Chien-Yi, Li, Hsin-Pai, Iang, Shan-Bei, Lin, Siao-Han, Yeh, Chau-Ting, Chao, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832723/
https://www.ncbi.nlm.nih.gov/pubmed/31614652
http://dx.doi.org/10.3390/v11100934
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author Hsu, Chao-Wei
Juang, Horng-Heng
Kuo, Chien-Yi
Li, Hsin-Pai
Iang, Shan-Bei
Lin, Siao-Han
Yeh, Chau-Ting
Chao, Mei
author_facet Hsu, Chao-Wei
Juang, Horng-Heng
Kuo, Chien-Yi
Li, Hsin-Pai
Iang, Shan-Bei
Lin, Siao-Han
Yeh, Chau-Ting
Chao, Mei
author_sort Hsu, Chao-Wei
collection PubMed
description Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HDV genotype 1, amber/W editing is controlled by HDAg and the RNA structure immediate vicinity and downstream of the editing site. Here, the effects of 20 mutants carrying an increased length of consecutive base-pairing at various sites in HDV RNA on amber/W site editing were examined. All nine mutants carrying genomic regions that formed up to 15 consecutive base pairs, which is also the maximum length observed in 41 naturally occurring HDV genomes, showed normal editing rate. However, mutants carrying a 16 or 17 consecutive base-paired antigenomic segment located as far as 114 nt upstream could increase editing efficiency, possibly by interfering with HDAg binding. These data show for the first time that extended base-pairing upstream of the amber/W site could increase HDV RNA editing efficiency. Furthermore, it appears that the naturally occurring HDV RNA structures have been selected for suboptimal amber/W RNA editing, which favors the HDV replication cycle.
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spelling pubmed-68327232019-11-25 Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing Hsu, Chao-Wei Juang, Horng-Heng Kuo, Chien-Yi Li, Hsin-Pai Iang, Shan-Bei Lin, Siao-Han Yeh, Chau-Ting Chao, Mei Viruses Article Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HDV genotype 1, amber/W editing is controlled by HDAg and the RNA structure immediate vicinity and downstream of the editing site. Here, the effects of 20 mutants carrying an increased length of consecutive base-pairing at various sites in HDV RNA on amber/W site editing were examined. All nine mutants carrying genomic regions that formed up to 15 consecutive base pairs, which is also the maximum length observed in 41 naturally occurring HDV genomes, showed normal editing rate. However, mutants carrying a 16 or 17 consecutive base-paired antigenomic segment located as far as 114 nt upstream could increase editing efficiency, possibly by interfering with HDAg binding. These data show for the first time that extended base-pairing upstream of the amber/W site could increase HDV RNA editing efficiency. Furthermore, it appears that the naturally occurring HDV RNA structures have been selected for suboptimal amber/W RNA editing, which favors the HDV replication cycle. MDPI 2019-10-11 /pmc/articles/PMC6832723/ /pubmed/31614652 http://dx.doi.org/10.3390/v11100934 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsu, Chao-Wei
Juang, Horng-Heng
Kuo, Chien-Yi
Li, Hsin-Pai
Iang, Shan-Bei
Lin, Siao-Han
Yeh, Chau-Ting
Chao, Mei
Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title_full Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title_fullStr Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title_full_unstemmed Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title_short Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
title_sort structural pattern differences in unbranched rod-like rna of hepatitis delta virus affect rna editing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832723/
https://www.ncbi.nlm.nih.gov/pubmed/31614652
http://dx.doi.org/10.3390/v11100934
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