ADARs regulate small RNAs mapped to edited sequences

Cellular RNAs containing double-stranded RNA (dsRNA) structures are subject to A-to-I RNA editing by the adenosine deaminases that act on RNA (ADARs). While A-to-I editing can alter mRNA coding potential, most editing is observed in non-coding sequences, the function of which remains poorly characterized. To correlate small RNA population with expression patterns of ADARs and hyperedited RNAs (editing-enriched regions: EERs) defined and characterized in a separate RNAseq analysis, we re-analyzed existing smallRNAseq datasets of a wildtype strain and a strain lacking ADARs (adr-1;adr-2). Analysis of primary siRNAs from mixed-stage worms revealed that ADARs impact siRNA biogenesis from EERs. We then analyzed primary and secondary RNAs mapping to EERs from embryo-stage or L4-stage worms and observed that ADAR effects on siRNA levels are dependent on developmental stage. For mixed-stage wildtype (N2) and adr-1;adr-2 samples, small RNAs with 5' monophosphates sequenced on Illumina HiSeq2000 (see GSE28888) were mapped to 1523 EERs defined in GSE79375, excluding those mapping to annotated miRNA or 21U-RNA loci. For embryo and L4-staged samples (from PMID: 21909095), small RNAseq using 5'phosphate independent protocols were likewise mapped to 1523 EERs, excluding those mapping to annotated miRNA or 21U-RNA loci. This series includes two samples re-analyzed from GSE28888 and eight samples re-analyzed from PubMed ID 21909095. These eight samples from PubMed ID 21909095 have not been deposited in GEO or SRA or any other public database and were obtained upon request from the authors. Included on this record are alignment files of reads aligned to EERs (in SAM format) and processed data for all re-analyzed samples.