Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism.

Casey, John L.; Bergmann, Katherine F.; Brown, Thomas L.; Gerin, John L.

doi:10.1073/pnas.89.15.7149

Cited by 128 publications

(138 citation statements)

References 34 publications

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“…The unbranched rod structure of the HDV genotype I antigenome presents the amber/W adenosine in such a structure, and has been shown by site-directed mutagenesis to be required for editing (Casey et al 1992;Polson et al 1996). However, for HDV genotype III, which is the most distantly related of the HDV clades and is associated with the most severe disease (Casey et al 1993;Manock et al 2000;Nakano et al 2001), the base-pairing in the immediate vicinity of the amber/W adenosine is disrupted in the unbranched rod structure.…”

Section: Introductionmentioning

confidence: 99%

“…Genomes synthesized from such edited antigenomes subsequently serve as templates for antigenomic sense mRNAs in which the amber stop codon has been replaced with a tryptophan codon. In mRNAs derived from edited antigenomes, an additional 19 or 20 codons are thereby translated to produce the long form of delta antigen, HDAg-L (Weiner et al 1988;Xia et al 1990;Casey et al 1992;Wang et al 1992). HDAg-L enables viral particle formation by interacting with the envelope protein of HBV, and inhibits replication (Kuo et al 1989;Chang et al 1991;Ryu et al 1992).…”

Section: Introductionmentioning

confidence: 99%

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The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

Linnstaedt

Kasprzak²,

Shapiro

et al. 2006

RNA

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RNA editing plays a critical role in the life cycle of hepatitis delta virus (HDV). The host editing enzyme ADAR1 recognizes specific RNA secondary structure features around the amber/W site in the HDV antigenome and deaminates the amber/W adenosine. A previous report suggested that a branched secondary structure is necessary for editing in HDV genotype III. This branched structure, which is distinct from the characteristic unbranched rod structure required for HDV replication, was only partially characterized, and knowledge concerning its formation and stability was limited. Here, we examine the secondary structures, conformational dynamics, and amber/W site editing of HDV genotype III RNA using a miniaturized HDV genotype III RNA in vitro. Computational analysis of this RNA using the MPGAfold algorithm indicated that the RNA has a tendency to form both metastable and stable unbranched secondary structures. Moreover, native polyacrylamide gel electrophoresis demonstrated that this RNA forms both branched and unbranched rod structures when transcribed in vitro. As predicted, the branched structure is a metastable structure that converts readily to the unbranched rod structure. Only branched RNA was edited at the amber/W site by ADAR1 in vitro. The structural heterogeneity of HDV genotype III RNA is significant because not only are both conformations of the RNA functionally important for viral replication, but the ratio of the two forms could modulate editing by determining the amount of substrate RNA available for modification.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

Linnstaedt

Kasprzak²,

Shapiro

et al. 2006

RNA

View full text Add to dashboard Cite

show abstract

“…Editing at the HDV amber/W site changes the amber stop codon of the short form of HDAg to a tryptophan codon. As a result, the virus produces two forms of HDAg that play critical roles in the replication cycle (Kuo et al 1989;Chang et al 1991;Casey et al 1992;Jayan and Casey 2002b).…”

Section: Introductionmentioning

confidence: 99%

The fraction of RNA that folds into the correct branched secondary structure determines hepatitis delta virus type 3 RNA editing levels

Linnstaedt

Kasprzak²,

Shapiro

et al. 2009

RNA

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RNA editing by the host RNA adenosine deaminase ADAR1 at the amber/W site of hepatitis delta virus RNA plays a central role in the viral replication cycle by affecting the balance between viral RNA synthesis and packaging. Previously, we found that HDV genotype III (HDV-3) RNA can form two secondary structures following transcription: an unbranched rod structure, which is characteristic of HDV, and a metastable branched structure that serves as the substrate for editing. The unstable nature of the branched editing substrate structure raised the possibility that structural dynamics of the RNA following transcription could determine the rate at which editing occurs. Here, editing and its control are examined in two HDV-3 isolates, from Peru and Ecuador. Analysis of editing in vitro by ADAR1 indicated that the branched structure formed by RNA derived from the Peruvian isolate is edited more efficiently than that from the Ecuadorian isolate. In contrast, in the context of replication, Peruvian RNA is edited less efficiently than RNA containing Ecuadorian sequences. Computational analyses of RNA folding using the massively parallel genetic algorithm (MPGAfold) indicated that the Peruvian RNA is less likely to form the branched structure required for editing than the Ecuadorian isolate. This difference was confirmed by in vitro transcription of these RNAs. Overall, our data indicate that HDV-3 controls RNA editing levels via (1) the fraction of the RNA that folds, during transcription, into the metastable branched structure required for editing and (2) the efficiency with which ADAR1 edits this branched substrate RNA.

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“…The modification of the GluR-2 exon requires the involvement of the neighbouring intron to form the required double-stranded RNA substrate structure (Melcher et al, 1996). The important question whether other still unveiled RNA editing events take place in other tissues where this ubiquitous enzyme is present remains to be answered.U-to-C conversion leading to the production of the viral protein p27 was suppossed to be the key step of RNA editing in hepatitis D virus (HDV) (Casey et al, 1992). However, a few years later it was found that the replication of this virus proceeds via an antigenome strand.…”

mentioning

confidence: 99%

“…U-to-C conversion leading to the production of the viral protein p27 was suppossed to be the key step of RNA editing in hepatitis D virus (HDV) (Casey et al, 1992). However, a few years later it was found that the replication of this virus proceeds via an antigenome strand.…”

mentioning

confidence: 99%

RNA editing in plant mitochondria, cytoplasmic male sterility and plant breeding

Araya¹

1998

Electron. J. Biotechnol.

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RNA editing in plant mitochondria is a post-transcriptional process involving the partial change of C residues into U. These C to U changes lead to the synthesis of proteins with an amino acid sequence different to that predicted from the gene. Proteins produced from edited mRNAs are more similar to those from organisms where this process is absent. This biochemical process involves cytidine deamination. The cytoplasmic male sterility (CMS) phenotype generated by the incompatibility between the nuclear and the mitochondrial genomes is an important agronomical trait which prevents inbreeding and favors hybrid production. The hypothesis that RNA editing leads to functional proteins has been proposed. This hypothesis was tested by constructing transgenic plants expressing a mitochondrial protein translated fom unedited mRNA. The transgenic "unedited" protein was addressed to the mitochondria leading to the appearance of mitochondrial dysfunction and generating the male sterile phenotype in transgenic tobacco plants. Male sterile plants were also obtained by expressing specifically a bacterial ribonuclease in the anthers. The economical benefits of artificially engineered male-sterile plants or carrying the (native) spontaneous CMS phenotype, implies the restoration to obtain fertile hybrids that will be used in agriculture. Restoration to fertility of transgenic plants was obtained either by crossing male-sterile plants carrying the "unedited" mRNA with plants carrying the same RNA, but in the antisense orientation or, in the case of plants expresing the ribonuclease, by crossing male-sterile plants with plants expressing an inhibitor specific of this enzyme. RNA editingGeneralities. The first time the word "RNA editing" was used, a dozen years ago, concerned the insertion or deletion of uridine residues in the mitochondrial RNAs of some trypanosomes. After that, RNA editing has been found in mitochondria and chloroplasts from land plants, in the mitochondria of some fungi, in the nuclear-cytoplasmic compartments from animal cells and in the genomes of some viruses. The RNA editing process involves in some cases the modification of residues in RNA or, in other cases, the insertion and/or deletion of nucleotides in messenger RNA (for some reviews see Adler and Hadjuk, 1994;Araya et al., 1994;Schuster and Brennicke, 1994;Scott, 1995;Smith et al., 1997;Stuart et al., 1997). The consequences of the RNA editing process are either the modification of the coded information for some amino acids or the generation of new initiation and/or termination codons. In organisms where RNA editing is active the protein sequence predicted from the gene may be different from that of the mRNA translated protein. While RNA editing is abondantly found in mitochondria and to a lesser extent in the chloroplast compartment of higher plants, it is not present in algae. RNA editing has also been descriibed in mitochondria from other organisms such as Physarum polycephalum, but not in yeast organelles. When detected in mammalian nuclear transcr...

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Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism.

Cited by 128 publications

References 34 publications

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

The fraction of RNA that folds into the correct branched secondary structure determines hepatitis delta virus type 3 RNA editing levels

RNA editing in plant mitochondria, cytoplasmic male sterility and plant breeding

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