Processing of Alu small RNAs by DICER/ADAR1 complexes and their RNAi targets

In addition to adenosine-to-inosine RNA editing activities, ADAR1 has been shown to have various RNA editing independent activities including modulation of RNAi efficacy. We previously reported that ADAR1 forms a heterodimer complex with DICER and facilitates processing of pre-miRNAs to mature miRNAs. In addition to miRNA synthesis, DICER is involved in processing of long dsRNAs into small RNAs (endo-siRNAs). Generation of retrotransposon-derived endo-siRNAs by DICER and their functions in regulation of transcripts in mouse oocyte transcripts has been previously reported. However, synthesis and functions of endo-siRNAs in somatic cells remain largely unknown. Here, we report that ADAR1 together with DICER generates endogenous small RNAs, Alu endo-siRNAs, by cleaving long double-stranded regions of inverted Alu repeats.