Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

doi:10.1093/nar/gkp604

Cited by 132 publications

(177 citation statements)

References 45 publications

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“…This meshes well with reports that RNA editing participates in host-viral interactions, such as the editing of the hepatitis C virus (HCV) genome by ADAR (Taylor et al 2005). Interestingly, some viruses have been able to take advantage of ADAR for their own purposes; endogenous ADAR has been shown to stimulate HIV-1 replication (Doria et al 2009). …”

Section: Discussionsupporting

confidence: 83%

RNA editing in the human ENCODE RNA-seq data

et al. 2012

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RNA-seq data can be mined for sequence differences relative to the reference genome to identify both genomic SNPs and RNA editing events. We analyzed the long, polyA-selected, unstranded, deeply sequenced RNA-seq data from the ENCODE Project across 14 human cell lines for candidate RNA editing events. On average, 43% of the RNA sequencing variants that are not in dbSNP and are within gene boundaries are A-to-G(I) RNA editing candidates. The vast majority of A-to-G(I) edits are located in introns and 3′ UTRs, with only 123 located in protein-coding sequence. In contrast, the majority of non–A-to-G variants (60%–80%) map near exon boundaries and have the characteristics of splice-mapping artifacts. After filtering out all candidates with evidence of private genomic variation using genome resequencing or ChIP-seq data, we find that up to 85% of the high-confidence RNA variants are A-to-G(I) editing candidates. Genes with A-to-G(I) edits are enriched in Gene Ontology terms involving cell division, viral defense, and translation. The distribution and character of the remaining non–A-to-G variants closely resemble known SNPs. We find no reproducible A-to-G(I) edits that result in nonsynonymous substitutions in all three lymphoblastoid cell lines in our study, unlike RNA editing in the brain. Given that only a fraction of sites are reproducibly edited in multiple cell lines and that we find a stronger association of editing and specific genes suggests that the editing of the transcript is more important than the editing of any individual site.

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Section: Discussionsupporting

confidence: 83%

RNA editing in the human ENCODE RNA-seq data

et al. 2012

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“…Furthermore, as an indirect antiviral mechanism, ADAR1 is critical for both embryonic and adult hematopoiesis, an essential system for maturation of all immune system cells (20,21,47). On the other hand, editing activity of ADARs can be harnessed by some viruses (e.g., HIV) to stimulate their replication, making ADAR1 as a proviral factor (48). The proviral effects of ADARs can be either dependent or independent of editing activity.…”

Section: Editome Imbalance In Hepatocellular Carcinomamentioning

confidence: 99%

“…ADAR1 has been shown able to inhibit the dsRNA-activated protein kinase, an important effecter of antiviral immunity by general inhibition of translation initiation, independent of editing activity (49). Moreover, ADAR1 can also directly edit virus RNA (e.g., HIV), and the editing activity is associated with enhanced virus infectivity (48). Whether ADAR1 also plays similar proviral roles in hepatocellular carcinoma still awaits further investigation.…”

Section: Editome Imbalance In Hepatocellular Carcinomamentioning

confidence: 99%

RNA Editome Imbalance in Hepatocellular Carcinoma

et al. 2014

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Adenosine-to-inosine conversion (A-to-I editing), a posttranscriptional modification on RNA, contributes to extensive transcriptome diversity. A-to-I editing is a hydrolytic deamination process, catalyzed by adenosine deAminase acting on double-stranded RNA (ADAR) family of enzymes. ADARs are essential for normal mammalian development, and disturbance in RNA editing has been implicated in various pathologic disorders, including cancer. Thanks to next-generation sequencing, rich databases of transcriptome evolution for cancer development at the resolution of single nucleotide have been generated. Extensive bioinformatic analysis revealed a complex picture of RNA editing change during transformation. Cancer displayed global hypoediting of Alurepetitive elements with gene-specific editing pattern. In particular, hepatocellular carcinoma editome is severely disrupted and characterized by hyper-and hypoediting of different genes, such as hyperedited AZIN1 (antizyme inhibitor 1) and FLNB (filamin B, b) and hypoedited COPA (coatomer protein complex, subunit a). In hepatocellular carcinoma, not only the recoding editing in exons, but also the editing in noncoding regions (e.g., Alu-repetitive elements and microRNA) displays such complex editing pattern with site-specific editing trend. In this review, we will discuss current research progress on the involvement of abnormal A-to-I editing in cancer development, more specifically on hepatocellular carcinoma. Cancer Res; 74(5); 1301-6. Ó2014 AACR.

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“…Even though both ADAR and ADARB1 are catalytically active (Nishikura 2010), ADAR is the best characterized, while the function of ADARB2 is unclear (Chen et al 2000). Like AICDA and APOBEC, ADAR-catalyzed editing has been implicated in a variety of biological processes, including AS (Solomon et al 2013), viral replication (Doria et al 2009), and immune development (Hartner et al 2009). Similarly to mRNA splicing, the determination of which cytidine or adenosine to deaminate is guided by consensus sequences, proximal to the edited nucleotide, which are then recognized by the mRNA binding motifs in the editing enzymes (Anant and Davidson 2000;Rosenberg et al 2011;Bahn et al 2012).…”

mentioning

confidence: 99%

The genetic basis for individual differences in mRNA splicing and APOBEC1 editing activity in murine macrophages

2013

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Alternative splicing and mRNA editing are known to contribute to transcriptome diversity. Although alternative splicing is pervasive and contributes to a variety of pathologies, including cancer, the genetic context for individual differences in isoform usage is still evolving. Similarly, although mRNA editing is ubiquitous and associated with important biological processes such as intracellular viral replication and cancer development, individual variations in mRNA editing and the genetic transmissibility of mRNA editing are equivocal. Here, we have used linkage analysis to show that both mRNA editing and alternative splicing are regulated by the macrophage genetic background and environmental cues. We show that distinct loci, potentially harboring variable splice factors, regulate the splicing of multiple transcripts. Additionally, we show that individual genetic variability at the Apobec1 locus results in differential rates of C-to-U(T) editing in murine macrophages; with mouse strains expressing mostly a truncated alternative transcript isoform of Apobec1 exhibiting lower rates of editing. As a proof of concept, we have used linkage analysis to identify 36 high-confidence novel edited sites. These results provide a novel and complementary method that can be used to identify C-to-U editing sites in individuals segregating at specific loci and show that, beyond DNA sequence and structural changes, differential isoform usage and mRNA editing can contribute to intra-species genomic and phenotypic diversity. [Supplemental material is available for this article.]Splicing is an obligatory step in the processing of both coding and noncoding RNA precursors (pre-RNA) to mature RNA, and is executed by a ribonucleoprotein megaparticle known as the spliceosome. Even though the sequential assembly of the spliceosome (Kornblihtt et al. 2013) can occur around any splice site that consists of consensus sequences recognized by the spliceosomal components, splice sites that conform better to a consensus sequence are strongly recognized and favored by the spliceosome complex. Besides the consensus sequences, the selection of optimal splice sites is regulated, in part, by a minimal set of conserved cis-acting GU and AG sequences at the 59 and 39 splice sites, respectively , and sequence elements known as intronic/exonic splicing enhancers and silencers

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Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

Cited by 132 publications

References 45 publications

RNA editing in the human ENCODE RNA-seq data

RNA editing in the human ENCODE RNA-seq data

RNA Editome Imbalance in Hepatocellular Carcinoma

The genetic basis for individual differences in mRNA splicing and APOBEC1 editing activity in murine macrophages

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