A circular trans-acting hepatitis delta virus ribozyme

Puttaraju, M.; Perrotta, Anne T.; Been, Michael D.

doi:10.1093/nar/21.18.4253

Cited by 66 publications

(56 citation statements)

References 48 publications

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“…If instead the sequence is divided within J1/2, the ribozyme is reconstituted through base pairing in PI (Fig. 3A, B, D-F; Been et al, 1992;Perrotta and Been, 1992;Puttaraju et al, 1993). However, because P1 is only 7 bp, the potential for targeting unique messages appears limited.…”

Section: Trans-acting Ribozymesmentioning

confidence: 99%

“…3D) is a composite of genomic and antigenomic pairings, loop and joining sequences and is unlikely to be functional if the proposed secondary structure is incorrect. Finally, a circular permutation, PDC7 , and a circular ribozyme, RCI (Puttaraju et al, 1993;Fig. 3 E and F), have been constructed and shown to behave as the linear ribozyme CDC200.…”

Section: Trans-acting Ribozymesmentioning

confidence: 99%

“…In terms of the cleavage reaction, this region may play little role other than to connect the two pairings, as it can be deleted entirely in the trans-reaction Puttaraju et al, 1993). Enzymatic and chemical probing in both ribozymes (Rosenstein and Been, 1991 ;Kumar et al, 1994;Perrotta, A. and Been, M. D., unpublished data) suggest that this region is very accessible and lacks well-defined stmcture.…”

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confidence: 99%

“…The possibility that P2 is transient and has to unpair in the course of the reaction, or that P2 is a feature of the folding pathway but not the catalytic structure is inconsistent with trans-acting ribozymes (Fig. 3), in which P2 is constrained by making it part of a hairpin with a stable tetraloop Puttaraju et al, 1993).…”

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confidence: 99%

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Self‐Cleaving Ribozymes of Hepatitis Delta Virus RNA

Been

Wickham

1997

European Journal of Biochemistry

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Hepatitis delta virus (HDV) is a small single-stranded RNA satellite of hepatitis B virus. Although it is a human pathogen, it shares a number of features with a subset of the small plant satellite RNA viruses, including self-cleaving sequences in the genomic and antigenomic sequences of the viral RNA. The selfcleaving sequence is critical to viral replication and is thought to function as a ribozyme in vivo to process the products of rolling-circle replication to unit-length molecules. A divalent cation is required for cleavage and while a structural role is implicated for metal ions, a more direct role for a metal ion in catalysishas not yet been proven. A minimal natural ribozyme sequence with proficient in viiro self-cleavage activity is about 85 nucleotides long and adopts a secondary structure with four paired regions (Pl-P4).The two pairings that define the 5' and 3' boundaries of the ribozyme, PI and P2, form an atypical pseudoknot arrangement. This secondary structure places a number of constraints on the possible tertiary folding of the sequence, which together with chemical probing, photo-cross-linking, mutagenesis and computer-assisted modeling provides clues to the three-dimensional structure. The data are consistent with a model in which the cleavage site, located at the 5' end of PI, is in close proximity to three singlestranded regions, consisting of a hairpin loop at the end of P3 and two sequences joining P1 to P4 and P4 to P2. While the natural forms of the HDV ribozymes appear to be prone to misfolding, biochemical and mutagenesis studies from a number of laboratories has allowed the production of trans-acting ribozymes and smaller more active cis-acting ribozymes, both of which will aid in further mechanistic and structural studies of this RNA.

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Section: Trans-acting Ribozymesmentioning

confidence: 99%

Section: Trans-acting Ribozymesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Self‐Cleaving Ribozymes of Hepatitis Delta Virus RNA

Been

Wickham

1997

European Journal of Biochemistry

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147

170

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“…82 Based on the permuted intron exon (PIE) method, a variety of circular RNAs up to the length of 1130 nts have been generated in vitro as well as in vivo, mostly in E.coli cells. 4,[83][84][85][86] Because RNA ligation for circularization is catalyzed by the intronic RNA, the system is also known as RNA cyclase ribozyme. 82 There is an early report on PIE mediated production of circular RNA in yeast.…”

Section: Ribozymes For Rna Circularizationmentioning

confidence: 99%

In vitro circularization of RNA

Müller

Appel

2016

RNA Biology

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Over the past 2 decades, different types of circular RNAs have been discovered in all kingdoms of life, and apparently, those circular species are more abundant than previously thought. Apart from circRNAs in viroids and viruses, circular transcripts have been discovered in rodents more than 20 y ago and recently have been reported to be abundant in many organisms including humans. Their exact function remains still unknown, although one may expect extensive functional studies to follow the currently dominant research into identification and discovery of circRNA by sophisticated sequencing techniques and bioinformatics. Functional studies require models and as such methods for preparation of circRNA in vitro. Here, we will review current protocols for RNA circularization and discuss future prospects in the field.Abbreviations: AMP, adenosine monophosphate; AppRNA, 5 0 -adenylated RNA; ATP, adenosine triphosphate; bp, base pair; CEV-A, citrus exocortis viroid strain A; circRNA, circular RNA; ciRNA, circular intronic RNA; CuAAC, cupper catalyzed azide alkyne cycloaddition; EDC, ethyl-3-(3 0 -dimethylaminopropyl)-carbodiimide; HIV, human immunodeficiency virus; IEciRNA, intron-exon circular RNA; nt, nucleotide; PIE, permuted intron exon; T4 Dnl, T4 DNA Ligase; T4 Rnl, T4 RNA Ligase

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RNAStability: Chemistry, Measurement and Modulation

McDowall

2008

Wiley Encyclopedia of Chemical Biology

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Molecules composed of RNA perform many roles that are vital for the life and reproduction of all cellular organisms and viruses, one of which is the role of messengers that carry from genes the information required for the production of protein. A typical feature of messenger RNA (mRNA) is its relative instability, which ensures that the production of any particular protein soon comes to an end when it is no longer required and synthesis of the message is downregulated. Moreover, while a transcript is being produced, its rate of decay is as important as its rate of synthesis in determining its cellular concentration and thus, to a large extent, its level of function. The turnover of mRNA, and indeed all other types of RNA, is mediated by multiple ribonucleases. The activity of these enzymes in cells can be inhibited rapidly by chemical treatments; thus, for many experimental systems their presence does not pose a significant barrier to the study of gene regulation at the RNA level. However, the development of RNA‐based therapeutics such as small interfering RNAs and aptamers has required the introduction of modifications to prevent their degradation by ribonucleases within the cells and body fluids of humans. This article describes the properties of RNA that make it susceptible to ribonucleases and the techniques used to determine the stability of RNA molecules. It also provides examples of how RNA stability in livings cells is being modulated for biotechnology and clinical applications, and it reviews the strategies that are being adopted to increase the in vivo stability of RNAs with therapeutic potential.

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A circular trans-acting hepatitis delta virus ribozyme

Cited by 66 publications

References 48 publications

Self‐Cleaving Ribozymes of Hepatitis Delta Virus RNA

Self‐Cleaving Ribozymes of Hepatitis Delta Virus RNA

In vitro circularization of RNA

RNAStability: Chemistry, Measurement and Modulation

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