Zhou, RuiCzech, BenjaminBrennecke, JuliusSachidanandam, RaviWohlschlegel, James A.Perrimon, NorbertHannon, Gregory J.2022-07-152009-10Zhou, Rui, Benjamin Czech, Julius Brennecke, Ravi Sachidanandam, James A. Wohlschlegel, Norbert Perrimon, Gregory J. Hannon. "Processing of Drosophila Endo-siRNAs Depends on a Specific Loquacious Isoform." RNA 15, no. 10 (2009): 1886-1895. DOI: 10.1261/rna.16113091355-83821469-9001https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372612Drosophila melanogaster expresses three classes of small RNAs, which are classified according to their mechanisms of biogenesis. MicroRNAs are ∼22–23 nucleotides (nt), ubiquitously expressed small RNAs that are sequentially processed from hairpin-like precursors by Drosha/Pasha and Dcr-1/Loquacious complexes. MicroRNAs usually associate with AGO1 and regulate the expression of protein-coding genes. Piwi-interacting RNAs (piRNAs) of ∼24–28 nt associate with Piwi-family proteins and can arise from single-stranded precursors. piRNAs function in transposon silencing and are mainly restricted to gonadal tissues. Endo-siRNAs are found in both germline and somatic tissues. These ∼21-nt RNAs are produced by a distinct Dicer, Dcr-2, and do not depend on Drosha/Pasha complexes. They predominantly bind to AGO2 and target both mobile elements and protein-coding genes. Surprisingly, a subset of endo-siRNAs strongly depend for their production on the dsRNA-binding protein Loquacious (Loqs), thought generally to be a partner for Dcr-1 and a cofactor for miRNA biogenesis. Endo-siRNA production depends on a specific Loqs isoform, Loqs-PD, which is distinct from the one, Loqs-PB, required for the production of microRNAs. Paralleling their roles in the biogenesis of distinct small RNA classes, Loqs-PD and Loqs-PB bind to different Dicer proteins, with Dcr-1/Loqs-PB complexes and Dcr-2/Loqs-PD complexes driving microRNA and endo-siRNA biogenesis, respectively.en-USResearch Subject Categories::NATURAL SCIENCES::Chemistry::Biochemistry::Functional genomicsProcessing of Drosophila Endo-siRNAs Depends on a Specific Loquacious IsoformJournal Article2022-07-1510.1261/rna.1611309