Novel splice variants of human ADAR2 mRNA: skipping of the exon encoding the dsRNA-binding domains, and multiple C-terminal splice sites

Gene. 2005 Dec 19:363:193-201. doi: 10.1016/j.gene.2005.07.028. Epub 2005 Nov 16.

Abstract

We report here two previously unknown alternative splice sites in the mRNA of human adenosine deaminase acting on RNA type 2 (ADAR2), an RNA editing enzyme. One splices out the whole of exon 2, which encodes two double-stranded RNA-binding domains (dsRBDs), resulting in a frameshift that introduces a stop codon in the downstream exon. This variant accounts for between 13% and 20% of the total ADAR2 mRNA in each developmental stage and brain region examined, even though its translated product is not expressed at levels that are detectable by Western blot analysis. The other new splice site is located in exon 9, 83 nucleotides downstream of the stop codon for the long C-terminus, resulting in a new 3' untranslated region (UTR) that is about 80 bp longer than the previously reported short C-terminus. The variant produced by this splice site has a stop codon at the same site as that in ADAR2 mRNA containing canonical exons 9 and 10, and is predicted to be translated as an enzymatically active ADAR2 protein. With these two additional splice sites, a total of 48 mRNA variants are theoretically possible, because each splicing event occurs independently. Among them, variants containing the long C-terminus are translated in human brains in situ, implying that alternative splicing in the 3' UTR of ADAR2 might regulate translational efficiency and mRNA stability in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenosine Deaminase / genetics*
  • Adult
  • Aged
  • Alternative Splicing*
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • DNA Primers
  • Exons*
  • Female
  • Gene Expression Profiling
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins

Substances

  • 3' Untranslated Regions
  • DNA Primers
  • RNA, Messenger
  • RNA-Binding Proteins
  • ADARB1 protein, human
  • Adenosine Deaminase