Adenosine to Inosine editing frequency controlled by splicing efficiency.
Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing.
Department of Cell- and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria.
Konstantin
K
Licht
Department of Cell- and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria.
Utkarsh
U
Kapoor
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
Elisa
E
Mayrhofer
Department of Cell- and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna 1030, Austria michael.jantsch@meduniwien.ac.at.
Michael F
MF
Jantsch
D000241:Adenosine / Q000235:genetics; D000243:Adenosine Deaminase / Q000235:genetics; D000818:Animals; D005091:Exons; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D007288:Inosine / Q000235:genetics; D007438:Introns / Q000235:genetics; D051379:Mice; D009690:Nucleic Acid Conformation; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics
D012322:RNA Precursors; D016601:RNA-Binding Proteins; D007288:Inosine; C000595356:ADAR protein, human; D000243:Adenosine Deaminase; D000241:Adenosine