Molecular basis for cytoplasmic RNA surveillance by uridylation-triggered decay in Drosophila.

The posttranscriptional addition of nucleotides to the 3 end of RNA regulates the maturation, function, and stability of RNA species in all domains of life. Here, we show that in flies, 3 terminal RNA uridylation triggers the processive, 3-to-5 exoribonucleolytic decay via the RNase II/R enzyme CG16940, a homolog of the human Perlman syndrome exoribonuclease Dis3l2. Together with the TUTase Tailor, dmDis3l2 forms the cytoplasmic, terminal RNA uridylation-mediated processing (TRUMP) complex that functionally cooperates in the degradation of structured RNA. RNA immunoprecipitation and high-throughput sequencing reveals a variety of TRUMP complex substrates, including abundant non-coding RNA, such as 5S rRNA, tRNA, snRNA, snoRNA, and the essential RNase MRP. Based on genetic and biochemical evidence, we propose a key function of the TRUMP complex in the cytoplasmic quality control of RNA polymerase III transcripts. Together with high-throughput biochemical characterization of dmDis3l2 and bacterial RNase R, our results imply a conserved molecular function of RNase II/R enzymes as readers of destabilizing posttranscriptional marksuridylation in eukaryotes and adenylation in prokaryotesthat play important roles in RNA surveillance.