Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4
RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Virus Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170223002010 |
| _version_ | 1797644773204426752 |
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| author | Chao-Wei Hsu Hsueh-Ying Hsu Chien-Hung Chen Mei Chao |
| author_facet | Chao-Wei Hsu Hsueh-Ying Hsu Chien-Hung Chen Mei Chao |
| author_sort | Chao-Wei Hsu |
| collection | DOAJ |
| description | RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation of RNA editing in HDV-2 and HDV-4 remains uncertain. Based on predictions of the unbranched rod-like RNA structures of HDV-2 and HDV-4, the editing site occurs as an A.C mismatch pair, surrounded by four base pairs upstream and two base pairs downstream of the editing site, respectively. To investigate HDV-2 and HDV-4 RNA editing, cultured cells were transfected with non-replicating editing reporters carrying wild-type sequences or specific mutations. The results revealed that the editing rates observed for wild-type HDV-2 and HDV-4 were fairly similar, albeit lower than that of HDV-1. Like HDV-1, both HDV-2 and HDV-4 showed a reduction in editing rate when the A.C mismatch pair and the immediately upstream base-paired region were disturbed. Notably, extending the downstream base-paired region from two to three or four (forming a structure identical to that of HDV-1) base pairs increased editing rate. Furthermore, we presented novel evidence that indicates the importance of the first bulge's size, located upstream of the editing site, and the base-pairing length within 7–13 and 28–39 nucleotides downstream of the editing site in influencing the HDV-4 editing rate. To summarize, our analyses suggest that the unbranched rod-like structures surrounding the editing site of HDV-2 and HDV-4 play a crucial role in regulating their RNA editing rates. |
| first_indexed | 2024-03-11T14:35:59Z |
| format | Article |
| id | doaj.art-ac2526f813de492ca46edc963988e95e |
| institution | Directory Open Access Journal |
| issn | 1872-7492 |
| language | English |
| last_indexed | 2024-03-11T14:35:59Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj.art-ac2526f813de492ca46edc963988e95e2023-10-31T04:08:52ZengElsevierVirus Research1872-74922023-12-01338199239Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4Chao-Wei Hsu0Hsueh-Ying Hsu1Chien-Hung Chen2Mei Chao3Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, TaiwanLiver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, TaiwanDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanLiver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Guishan, Taoyang 33302, Taiwan; Department of Microbiology and Immunology and Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang 33302, Taiwan; Corresponding author at: Department of Microbiology and Immunology, Chang Gung University, No.259, Wenhua 1st Rd., Guishan, Taoyang 33302, Taiwan.RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation of RNA editing in HDV-2 and HDV-4 remains uncertain. Based on predictions of the unbranched rod-like RNA structures of HDV-2 and HDV-4, the editing site occurs as an A.C mismatch pair, surrounded by four base pairs upstream and two base pairs downstream of the editing site, respectively. To investigate HDV-2 and HDV-4 RNA editing, cultured cells were transfected with non-replicating editing reporters carrying wild-type sequences or specific mutations. The results revealed that the editing rates observed for wild-type HDV-2 and HDV-4 were fairly similar, albeit lower than that of HDV-1. Like HDV-1, both HDV-2 and HDV-4 showed a reduction in editing rate when the A.C mismatch pair and the immediately upstream base-paired region were disturbed. Notably, extending the downstream base-paired region from two to three or four (forming a structure identical to that of HDV-1) base pairs increased editing rate. Furthermore, we presented novel evidence that indicates the importance of the first bulge's size, located upstream of the editing site, and the base-pairing length within 7–13 and 28–39 nucleotides downstream of the editing site in influencing the HDV-4 editing rate. To summarize, our analyses suggest that the unbranched rod-like structures surrounding the editing site of HDV-2 and HDV-4 play a crucial role in regulating their RNA editing rates.http://www.sciencedirect.com/science/article/pii/S0168170223002010Hepatitis delta virusGenotypeRNA editingADAR1Delta antigen |
| spellingShingle | Chao-Wei Hsu Hsueh-Ying Hsu Chien-Hung Chen Mei Chao Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 Virus Research Hepatitis delta virus Genotype RNA editing ADAR1 Delta antigen |
| title | Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 |
| title_full | Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 |
| title_fullStr | Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 |
| title_full_unstemmed | Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 |
| title_short | Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4 |
| title_sort | unbranched rod like rna is required for rna editing of hepatitis delta virus genotype 2 and genotype 4 |
| topic | Hepatitis delta virus Genotype RNA editing ADAR1 Delta antigen |
| url | http://www.sciencedirect.com/science/article/pii/S0168170223002010 |
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