HDV Ribozymes

Department of Biochemistry, Duke University Medical Center, Durham, NC, USA [email protected]

1 Introduction 48

2 Sequence Requirements 48

2.1 Defining a Ribozyme Sequence 48

2.2 Two HDV Ribozymes 50

3 Ribozyme Structure 50

4 Cleavage Reaction 52

5 Catalytic Strategies 54

5.1 In-line Orientation 54

5.2 Divalent Metal Ion 55

5.3 An Active Site Nucleobase 57

5.4 Site of Action of the Catalytic Cytosine 59

6 Conclusion 60

References 61

Abstract The self-cleaving RNA sequences, or ribozymes, in the genomic and antige-nomic strands of hepatitis delta virus (HDV) RNA fold into structures that are similar to each other but distinct from those of small ribozymes associated with the RNA repli-cons that infect plants. HDV ribozymes have provided a tractable system for studying the mechanism of catalytic RNA, and results of biochemical and structural studies on the HDV ribozymes, from a number of labs, have enhanced our understanding and expanded our thinking about the potential for catalytic roles of RNA side chains. The results of these studies are consistent with models suggesting that both an active-site cytosine and a divalent metal ion have catalytic roles in facilitating the cleavage reaction in the HDV ribozymes. Despite recent advances, details about the catalytic mechanism of the HDV ribozyme continue to be debated, and these ribozymes should serve as a good system for further study.

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