RRC ID 45882
Author Wheeler EC, Washburn MC, Major F, Rusch DB, Hundley HA.
Title Noncoding regions of C. elegans mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript.
Journal RNA Biol
Abstract ADARs (Adenosine deaminases that act on RNA) "edit" RNA by converting adenosines to inosines within double-stranded regions. The primary targets of ADARs are long duplexes present within noncoding regions of mRNAs, such as introns and 3' untranslated regions (UTRs). Because adenosine and inosine have different base-pairing properties, editing within these regions can alter splicing and recognition by small RNAs. However, despite numerous studies identifying multiple editing sites in these genomic regions, little is known about the extent to which editing sites co-occur on individual transcripts or the functional output of these combinatorial editing events. To begin to address these questions, we performed an ultra-deep sequencing analysis of 4 Caenorhabditis elegans 3' UTRs that are known ADAR targets. Synchronous editing events were determined for the long duplexes in vivo. Furthermore, the validity of each editing event was confirmed by sequencing the same regions of mRNA from worms that lack A-to-I editing. This analysis identified a large number of editing sites that can occur within each 3' UTR, but interestingly, each individual transcript contained only a small fraction of these A-to-I editing events. In addition, editing patterns were not random, indicating that an editing event can affect the efficiency of editing at subsequent adenosines. Furthermore, we identified specific sites that can be both positively and negatively correlated with additional sites leading to mutually exclusive editing patterns. These results suggest that editing in noncoding regions is selective and hyper-editing of cellular RNAs is rare.
Volume 12(2)
Pages 162-74
Published 2015-1-1
DOI 10.1080/15476286.2015.1017220
PMID 25826568
PMC PMC4615841
MeSH 3' Untranslated Regions Adenosine / metabolism* Adenosine Deaminase / genetics Adenosine Deaminase / metabolism* Animals Base Pairing Base Sequence Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Deamination Exons High-Throughput Nucleotide Sequencing Inosine / metabolism* Introns Molecular Sequence Data Nucleic Acid Conformation Open Reading Frames RNA Editing* RNA, Helminth / genetics RNA, Helminth / metabolism*
IF 5.477
Times Cited 7
C.elegans tm668