| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 103 === Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus. HDV is unique in having an unbranched rod-like circular RNA with ribozyme activity, and a double rolling-circle replication strategy utilizing host RNA polymerases. During HDV replication cycle, host adenosine deaminase ADAR1-mediated RNA editing occurs at the amber/W site, which in turn changes the UAG stop codon into UGG tryptophan coden and results in the production of two forms of the delta entigen. The small one supports HDV RNA replication, while the large one is crucial for virion assembly. Previous study have show that the degree of base-pairing 3’ to the amber/W site plays a pivotal role in ADAR editing. Here, I showed, for the first time, that RNA structure located at 5’ of the amber/W site played an important role in amber/W editing. Two series of HDV mutants carrying different degree of base-pairing at different distance 5’ to the amber/W site were constructed. The data indicated that the length of contiguous base pairs located 5’ of the amber/W site affected the level of amber/W editing. HDV mutants carrying 17 contiguous base-paired regions located at 12-, 50-, and 77-nt 5’ from the amber/W site promoted amber/W editing. Moreover, we also discovered three more potential editing sites (nt 1375 CU, nt 218 AG, and nt 219 UC) in HDV-1 Italian strain, but not in the HDV-1 American and Taiwanese HDV-2 and HDV-4 clones. Taken together, my data provided a better understanding of molecular mechanism of HDV RNA editing in production of viral proteins and generation of genomic diversity.
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