Hepatitis Delta Virus Minimal Substrates Competent for Editing by ADAR1 and ADAR2

Sato, Shuji; Wong, Sharon; Lazinski, David W.

doi:10.1128/jvi.75.18.8547-8555.2001

Cited by 64 publications

(87 citation statements)

References 34 publications

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“…The HDV antigenomic strand has a ribozyme element located across from the genomic ribozyme ( Fig. 1), is known to bind PKR (Robertson et al 1996), and is also known to be edited (Polson et al 1996;Sato et al 2001) by an adenosine deaminase activated by RNA (ADAR), another dsRBM-containing cellular protein (Melcher et al 1996). We confirm here that these biological functions of the HDV antigenomic strand are likely to involve local tertiary structure.…”

Section: Introductionsupporting

confidence: 72%

“…The HDV antigenomic RNA strand-in its role as mRNA for HDV antigen-undergoes RNA editing in vivo during HDV's life cycle so that it encodes shorter and longer versions of the antigen that share a common amino terminus. Recent studies have shown that in all likelihood, a host ADAR enzyme catalyzes this step (Polson et al 1996;Sato et al 2001). Because, like PKR, the ADAR enzymes utilize the dsRBM motif in RNA recognition, it is possible that recognition FIGURE 4.…”

Section: Activation Of Host Pkr Hdv Antigen Is Phosphorylatedmentioning

confidence: 99%

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Recurring features of local tertiary structural elements in RNA molecules exemplified by hepatitis D virus RNA

Circle

Lyons²,

Neel³

et al. 2003

RNA

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Elements of local tertiary structure in RNA molecules are important in understanding structure-function relationships. The loop E motif, first identified in several eukaryotic RNAs at functional sites which share an exceptional propensity for UV crosslinking between specific bases, was subsequently shown to have a characteristic tertiary structure. Common sequences and secondary structures have allowed other examples of the E-loop motif to be recognized in a number of RNAs at sites of protein binding or other biological function. We would like to know if more elements of local tertiary structure, in addition to the E-loop, can be identified by such common features. The highly structured circular RNA genome of the hepatitis D virus (HDV) provides an ideal test molecule because it has extensive internal structure, a UV-crosslinkable tertiary element, and specific sites for functional interactions with proteins including host PKR. We have now found a UV-crosslinkable element of local tertiary structure in antigenomic HDV RNA which, although differing from the E-loop, has a very similar pattern of sequence and secondary structure to the UV-crosslinkable element found in the genomic strand. Despite the fact that the two structures map close to one another, the sequences comprising them are not the templates for each other. Instead, the template regions for each element are additional sites for potential higher order structure on their respective complementary strands. This wealth of recurring sequences interspersed with base-paired stems provides a context to examine other RNA species for such features and their correlations with biological function.

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Section: Introductionsupporting

confidence: 72%

Section: Activation Of Host Pkr Hdv Antigen Is Phosphorylatedmentioning

confidence: 99%

Recurring features of local tertiary structural elements in RNA molecules exemplified by hepatitis D virus RNA

Circle

Lyons²,

Neel³

et al. 2003

RNA

View full text Add to dashboard Cite

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“…2A; Sato et al 2001;Wong et al 2001Wong et al , 2003Wong and Lazinski 2002;Desterro et al 2003). Using similar vector constructs, we here show that the observation is not a translational phenomenon but originates from a heterologous splicing event between a vectorencoded 59-splice site (SV40 intron) and the previously unknown 39-splice site of the intron in exon 2 of ADAR1 (Fig.…”

Section: Alternatively Spliced Adar1-a Is Translated But Evades Nmdmentioning

confidence: 81%

Alternative splicing of the ADAR1 transcript in a region that functions either as a 5′-UTR or an ORF

Lykke‐Andersen¹,

Piñol-Roma²,

Kjems³

2007

RNA

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The ADAR enzymes mediate the hydrolytic deamination of adenosines in specific RNA substrates and thereby diversify both the transcriptome and the proteome in metazoan species. Three promoters drive the transcription from the ADAR1 gene yielding the ADAR1-A, -B, and -C transcripts, which, in turn, lead to the production of two protein isoforms, namely, iADAR1 and cADAR1. In this study, we establish the presence of a previously unidentified alternative intron within the 59-end of the common second exon of mRNAs encoding ADAR1 in primate species-a region that can function either as a 59-UTR or an ORF. In addition, it is shown that the relative expression of the three promoter-specific ADAR1 transcripts is tissue specific and that the novel intron is excised from all transcripts, but at different relative levels indicating a specific regulation of the alternative splicing. Finally, possible functional consequences of the splicing are investigated. From these studies, we conclude that the alternatively spliced ADAR1-A transcript is immune to nonsense-mediated decay although it is a potential substrate. Moreover, this transcript is associated with translating ribosomes, which suggests that a truncated version of iADAR1 is expressed.

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“…The latter result, as well as the fact that mammalian liver contains high levels of ADAR1 but not ADAR2, suggests that ADAR1 deaminates the amber/W site in vivo. However, both enzymes are capable of editing the amber/W site (93).…”

Section: Hepatitis Delta Virus-thementioning

confidence: 99%

RNA Editing by Adenosine Deaminases That Act on RNA

Bass

2002

Annu. Rev. Biochem.

1,217

1,303

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ADARs are RNA editing enzymes that target double-stranded regions of nuclear-encoded RNA and viral RNA. These enzymes are particularly abundant in the nervous system, where they diversify the information encoded in the genome, for example, by altering codons in mRNAs. The functions of ADARs in known substrates suggest that the enzymes serve to fine-tune and optimize many biological pathways, in ways that we are only starting to imagine. ADARs are also interesting in regard to the remarkable double-stranded structures of their substrates and how enzyme specificity is achieved with little regard to sequence. This review summarizes ongoing investigations of the enzyme family and their substrates, focusing on biological function as well as biochemical mechanism.

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Hepatitis Delta Virus Minimal Substrates Competent for Editing by ADAR1 and ADAR2

Cited by 64 publications

References 34 publications

Recurring features of local tertiary structural elements in RNA molecules exemplified by hepatitis D virus RNA

Recurring features of local tertiary structural elements in RNA molecules exemplified by hepatitis D virus RNA

Alternative splicing of the ADAR1 transcript in a region that functions either as a 5′-UTR or an ORF

RNA Editing by Adenosine Deaminases That Act on RNA

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