title: Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform.
abstract: Drosophila melanogaster expresses three classes of small RNAs, which are classified according to their mechanisms of biogenesis. MicroRNAs are approximately 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 approximately 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 approximately 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.
authors.affiliation: Harvard Medical School, Department of Genetics, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Benjamin
authors.initials: B
authors.lastname: Czech
authors.forename: Julius
authors.initials: J
authors.lastname: Brennecke
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements; D004331:Drosophila melanogaster / Q000235:genetics*; D020868:Gene Silencing; D005854:Germ Cells; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D034741:RNA, Small Interfering