Loquacious, a Dicer Partner Protein, Functions in Both the MicroRNA and siRNA Pathways

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding protein partners that change what substrates Dicer uses and where within the substrate they dice. In the fruit fly Drosophila melanogaster, different Dicer enzymes produce microRNAs (miRNAs) and small interfering RNAs (siRNAs): Dicer-1 produces miRNAs from pre-miRNAs, while Dicer-2 generates siRNAs from long double-stranded RNA. Flies produce four Dicer partner proteins-one encoded by the r2d2 locus and three by loquacious (loqs). Alternative splicing of loqs generates Loqs-PA, Loqs-PB, and Loqs-PD. Loqs-PA and Loqs-PB bind to Dicer-1 and assist miRNA biogenesis by increasing substrate affinity or enzyme turnover. Loqs-PB also alters the size of some miRNAs, generating isoforms with seed sequences and target specificities distinct from those that would be made by Dicer-1 alone or Dicer-1 bound to Loqs-PA. Loqs-PD binds Dicer-2, promoting the production of both endogenous and exogenous siRNAs by increasing substrate affinity. In this chapter, we will discuss the diverse functions loqs plays in small silencing RNA pathways.