Dataset Information

Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G.

ABSTRACT: APOBEC3A and APOBEC3G cytidine deaminases inhibit viruses and endogenous retrotransposons. We recently demonstrated the novel cellular C-to-U RNA editing function of APOBEC3A and APOBEC3G. Both enzymes deaminate single-stranded DNAs at multiple TC or CC nucleotide sequences, but edit only a select set of RNAs, often at a single TC or CC nucleotide sequence. To examine the specific site preference for APOBEC3A and -3G-mediated RNA editing, we performed mutagenesis studies of the endogenous cellular RNA substrates of both proteins. We demonstrate that both enzymes prefer RNA substrates that have a predicted stem-loop with the reactive C at the 3'-end of the loop. The size of the loop, the nucleotides immediately 5' to the target cytosine and stability of the stem have a major impact on the level of RNA editing. Our findings show that both sequence and secondary structure are preferred for RNA editing by APOBEC3A and -3G, and suggest an explanation for substrate and site-specificity of RNA editing by APOBEC3A and -3G enzymes.

SUBMITTER: Sharma S

PROVIDER: S-EPMC5723131 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G.

Sharma Shraddha S Baysal Bora E BE

PeerJ 20171206

APOBEC3A and APOBEC3G cytidine deaminases inhibit viruses and endogenous retrotransposons. We recently demonstrated the novel cellular C-to-U RNA editing function of APOBEC3A and APOBEC3G. Both enzymes deaminate single-stranded DNAs at multiple TC or CC nucleotide sequences, but edit only a select set of RNAs, often at a single TC or CC nucleotide sequence. To examine the specific site preference for APOBEC3A and -3G-mediated RNA editing, we performed mutagenesis studies of the endogenous cellul ...[more]

PMID: 29230368

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Project description:RNA editing is a co-transcriptional modification that increases the molecular diversity, alters secondary structure and protein coding sequences by changing the sequence of transcripts. The most common RNA editing modification is the single base substitution (A?I) that is catalyzed by the members of the Adenosine deaminases that act on RNA (ADAR) family. Typically, editing sites are identified as RNA-DNA-differences (RDDs) in a comparison of genome and transcriptome data from next-generation sequencing experiments. However, a method for robust detection of site-specific editing events from replicate RNA-seq data has not been published so far. Even more surprising, condition-specific editing events, which would show up as differences in RNA-RNA comparisons (RRDs) and depend on particular cellular states, are rarely discussed in the literature.We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples. The performance of JACUSA has been carefully evaluated and compared to other variant callers in an in silico benchmark. JACUSA outperforms other algorithms in terms of the F measure, which combines precision and recall, in all benchmark scenarios. This performance margin is highest for the RNA-RNA comparison scenario. We further validated JACUSA's performance by testing its ability to detect A?I events using sequencing data from a human cell culture experiment and publicly available RNA-seq data from Drosophila melanogaster heads. To this end, we performed whole genome and RNA sequencing of HEK-293 cells on samples with lowered activity of candidate RNA editing enzymes. JACUSA has a higher recall and comparable precision for detecting true editing sites in RDD comparisons of HEK-293 data. Intriguingly, JACUSA captures most A?I events from RRD comparisons of RNA sequencing data derived from Drosophila and HEK-293 data sets.Our software JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In practice, JACUSA shows higher recall and comparable precision in detecting A?I sites from RNA-DNA comparisons, while showing higher precision and recall in RNA-RNA comparisons.

Dataset Information

Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G.

Publications

Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G.

Similar Datasets

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