title: Genome-wide profiling of the C. elegans dsRNAome.
abstract: Recent studies hint that endogenous dsRNA plays an unexpected role in cellular signaling. However, a complete understanding of endogenous dsRNA signaling is hindered by an incomplete annotation of dsRNA-producing genes. To identify dsRNAs expressed in Caenorhabditis elegans, we developed a bioinformatics pipeline that identifies dsRNA by detecting clustered RNA editing sites, which are strictly limited to long dsRNA substrates of Adenosine Deaminases that act on RNA (ADAR). We compared two alignment algorithms for mapping both unique and repetitive reads and detected as many as 664 editing-enriched regions (EERs) indicative of dsRNA loci. EERs are visually enriched on the distal arms of autosomes and are predicted to possess strong internal secondary structures as well as sequence complementarity with other EERs, indicative of both intramolecular and intermolecular duplexes. Most EERs were associated with protein-coding genes, with ∼1.7% of all C. elegans mRNAs containing an EER, located primarily in very long introns and in annotated, as well as unannotated, 3' UTRs. In addition to numerous EERs associated with coding genes, we identified a population of prospective noncoding EERs that were distant from protein-coding genes and that had little or no coding potential. Finally, subsets of EERs are differentially expressed during development as well as during starvation and infection with bacterial or fungal pathogens. By combining RNA-seq with freely available bioinformatics tools, our workflow provides an easily accessible approach for the identification of dsRNAs, and more importantly, a catalog of the C. elegans dsRNAome.
authors: Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112-5650, USA.
authors: Joseph M
authors: JM
authors: Whipple
authors: Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112-5650, USA.
authors: Osama A
authors: OA
authors: Youssef
authors: Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112-5650, USA.
authors: P Joseph
authors: PJ
authors: Aruscavage
authors: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112-5775, USA.
authors: David A
authors: DA
authors: Nix
authors: Division of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Changjin
authors: C
authors: Hong
authors: Division of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: W Evan
authors: WE
authors: Johnson
authors: Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112-5650, USA.
authors: Brenda L
authors: BL
authors: Bass
mesh_terms: D020413:3' Untranslated Regions; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D049751:Genome, Helminth; D007438:Introns; D008969:Molecular Sequence Data; D017393:RNA Editing; D012330:RNA, Double-Stranded / Q000235:genetics*; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D012330:RNA, Double-Stranded; D000243:Adenosine Deaminase
keywords: 3′ UTR; RNA editing; dsRNA; hyperediting; long introns