Normal microRNA Maturation and Germ-Line Stem Cell Maintenance Requires Loquacious, a Double-Stranded RNA-Binding Domain Protein

By Klaus Förstemann, Yukihide Tomari, T. Du, Vasily V. Vagin, Ahmet M. Denli, D. Bratu, Carla A. Klattenhoff, W. Theurkauf, Phillip D. Zamore. PLoS Biology, 2005

605 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a49d9dd8ae715f4bfa25426f843d4f33671ff3b1

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Citations in the corpus

microPrimer: the biogenesis and function of microRNA (2005, background): “…makes a pair of cuts that defines the other end of the mature miRNA, liberating an ~21-nucleotide RNA duplex (Bernstein et al., 2001; Grishok et al., 2001; Hutvagner et al., 2001; Ketting et al., 2001; Chendrimada et al., 2005; Forstemann et al., 2005; Jiang et al., 2005; Saito et al., 2005).”
Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. (2006, background): “…silencing pathway triggered by double-stranded RNA (dsRNA) (Tomari and Zamore 2005). dsRNA is processed by Dicer to short interfering RNA (siRNA) (21–23 nucleotides [nt] in length), unwound, and loaded onto the RNA-induced silencing complex (RISC) as a single-stranded guide siRNA (Hammond 2005).”
The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. (2007, positive): “GFP, Drosha, Dicer-1, loqs, and Dicer-2 dsRNAs were produced using published pLitmus templates (Forstemann et al., 2005) and T7 Megascript (Ambion).”
The role of PACT in the RNA silencing pathway (2006, background): “When Loqs was depleted by RNAi in the Drosophila S2 cell line, the mature miRNA level was reduced, while pre- miRNAs accumulated, indicating that Loqs is required for the pre-miRNA cleavage event (Forstemann et al, 2005; Jiang et al, 2005; Saito et al, 2005).”
Modulation of microRNA processing and expression through RNA editing by ADAR deaminases (2006, background): “Cytoplasmic Dicer, together with a dsRNA-binding protein, TRBP, then processes the pre-miRNAs into 20- to 22-nt short interfering RNA (siRNA)-like duplexe”
An endogenous small interfering RNA pathway in Drosophila (2008, background): “14) but a strong requirement for the Dcr-1 partner Loquacious 1,4,5 .”