Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein.
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.
Förstemann
Klaus
K
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Tomari
Yukihide
Y
Du
Tingting
T
Vagin
Vasily V
VV
Denli
Ahmet M
AM
Bratu
Diana P
DP
Klattenhoff
Carla
C
Theurkauf
William E
WE
Zamore
Phillip D
PD
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D005260:Female; D005854:Germ Cells / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D020365:RNA Helicases / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*
D029721:Drosophila Proteins; C503213:Loqs protein, Drosophila; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; C493335:drosha protein, Drosophila; D020365:RNA Helicases