Interdisciplinary Graduate Program
Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
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.
DOI of Published Version
PLoS Biol. 2005 Jul;3(7):e236. Epub 2005 May 24. Link to article on publisher's site
Forstemann, Klaus; Tomari, Yukihide; Du, Tingting; Vagin, Vasily V.; Denli, Ahmet M.; Bratu, Diana P.; Klattenhoff, Carla Andrea; Theurkauf, William E.; and Zamore, Phillip D., "Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein" (2005). GSBS Student Publications. 300.