Vesicular stomatitis virus defective interfering particles can contain extensive genomic sequence rearrangements and base substitutions

A minor fraction of basic fibroblast growth factor mRNA is deaminated in Xenopus stage VI and matured oocytes

“…Adenosine deaminases that act on RNA (ADARs) catalyze the conversion of adenosine to inosine within double-stranded regions of RNA+ ADAR activity has been found in every metazoan tested and in all tissues assayed+ Initially described as an unwinding/modifying activity from Xenopus laevis, ADAR1 (previously called dsRAD or DRADA) is one member of a growing family that together are responsible for the adenosine deaminase activity observed in metazoan tissues (reviewed in Bass, 1997)+ ADARs have been implicated in two very different types of adenosine deamination in vivo: highly selective RNA editing and hypermutation+ Highly selective RNA editing by ADARs is a process in which only one or very few adenosines within an RNA are deaminated+ Conversely, hypermutation is a less selective process that typically leads to deamination of ;50% of the adenosines in a given RNA+ Accessory factors that provide selectivity have not been identified+ Rather, it has been suggested that selectivity is determined by the structure and stability of the RNA substrate (Bass, 1997)+ Consistent with this hypothesis, stable, perfectly basepaired duplexes of Ն50 nt show up to 50% deamination, while shorter, less stable dsRNA molecules are deaminated much more selectively (Nishikura et al+, 1991;Polson & Bass, 1994)+ Highly selective RNA editing by ADARs has been observed in the transcripts encoding certain glutamate receptor subunits (Maas et al+, 1997) and the serotonin receptor subtype, 5-HT 2c R (Burns et al+, 1997)+ In these RNAs, selective adenosine-to-inosine changes result in amino acid changes that have important biological consequences+ Likewise, a single specific adenosineto-inosine change in the antigenome of hepatitis delta virus results in the conversion of an amber stop codon to a tryptophan, allowing the virus to make two essential proteins from a single open reading frame (Polson et al+, 1996)+ Hypermutation of adenosines in vivo has been implicated in persistent infection of measles virus (Billeter et al+, 1994;Cattaneo, 1994)+ In addition, extensive A-to-G changes have been observed in cDNAs derived from vesicular stomatitis virus (O'Hara et al+, 1984), several other negative strand RNA viruses (Murphy et al+, 1991;Rueda et al+, 1994), and polyoma virus, a DNA virus (Kumar & Carmichael, 1997)+ A-to-G transitions are indicative of adenosine deamination because inosine, like guanosine, prefers to base-pair with cytidine+ Consequently, after reverse transcription and second strand DNA synthesis, an inosine in an RNA appears as a guanosine in the cDNA+ Recently, a single cDNA of the 4f-rnp gene from Drosophila was also observed to contain extensive A-to-G changes (Petschek et al+, 1996)+ This is the first report of a cellular RNA that appears to be deaminated by hypermutation, but certainly many others could exist+ In fact, a number of eukaryotic genes have an overlapping open reading frame (ORF) on the antisense or noncoding DNA strand (reviewed in Dolnick, 1997)+ Transcription of opposite strands at the same genomic locus produces RNA transcripts containing an extended region of complementary sequence+ If these RNAs hybridized, th...…”

Elevated activity of the large form of ADAR1 in vivo: Very efficient RNA editing occurs in the cytoplasm

“…www.rnajournal.org RNA viruses, including measles virus (Cattaneo 1994), parainfluenza virus (Murphy et al 1991), and vesicular stomatitis virus (O'Hara et al 1984). Because expression of ADAR1-L can be induced by interferon, it is plausible that this enzyme, as part of the cellular immune response, could be responsible for deaminating cytoplasmic viral dsRNAs.…”

RNA Editing by Adenosine Deaminases That Act on RNA

“…In most other cases the question of whether ADARs are responsible for the observed sequence transitions has not been directly addressed, but indirect evidence makes it likely. For example, when the sequence contexts of the observed A to G or U to C changes have been published (77)(78)(79)82), it is clear that the changes occur at sites with nearest neighbors preferred by ADARs (83) (see Preferences, below). Except for the examples discussed below, the viral hypermutations have not been correlated with a functional consequence.…”

“…In some cases it is clear that the virus, or viral transcripts, form intramolecular hairpins (78,79) or interact with an antisense molecule (80). In other cases how the dsRNA forms is unclear.…”