Interdisciplinary Graduate Program
Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
Medical Subject Headings
Alternative Splicing; Amino Acid Sequence; Animals; Animals, Genetically Modified; Base Sequence; Drosophila Proteins; Drosophila melanogaster; Female; Germ Cells; Male; MicroRNAs; Molecular Sequence Data; RNA Helicases; RNA Interference; RNA-Binding Proteins; Ribonuclease III; Stem Cells
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences
microRNAs (miRNAs) are single-stranded, 21- to 23-nucleotide cellular RNAs that control the expression of cognate target genes. Primary miRNA (pri-miRNA) transcripts are transformed to mature miRNA by the successive actions of two RNase III endonucleases. Drosha converts pri-miRNA transcripts to precursor miRNA (pre-miRNA); Dicer, in turn, converts pre-miRNA to mature miRNA. Here, we show that normal processing of Drosophila pre-miRNAs by Dicer-1 requires the double-stranded RNA-binding domain (dsRBD) protein Loquacious (Loqs), a homolog of human TRBP, a protein first identified as binding the HIV trans-activator RNA (TAR). Efficient miRNA-directed silencing of a reporter transgene, complete repression of white by a dsRNA trigger, and silencing of the endogenous Stellate locus by Suppressor of Stellate, all require Loqs. In loqs(f00791) mutant ovaries, germ-line stem cells are not appropriately maintained. Loqs associates with Dcr-1, the Drosophila RNase III enzyme that processes pre-miRNA into mature miRNA. Thus, every known Drosophila RNase-III endonuclease is paired with a dsRBD protein that facilitates its function in small RNA biogenesis.
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Citation: PLoS Biol. 2005 Jul;3(7):e236. Epub 2005 May 24. Link to article on publisher's site