My theme of small RNA regulatory mechanisms began with my graduate studies. I provided the first molecular evidence that Drosophila CMTR1 (dCMTR1) is a positive regulator of the small RNA pathway associated with Ago2 and has broad roles in small RNA-mediated gene silencing pathway. This is the first characterization of miRNA cap1-methyltransferase activity of CMTR1 in Drosophila as well as first demonstration of involvement of dCMTR1 in RNAi pathway. I found that the catalytic activity of dCMTR1 was involved in the biogenesis of small interfering RNAs (siRNAs) but not microRNAs. Moreover, I found that loss of dCMTR1 function impaired RISC assembly by inhibiting the unwinding of Ago2-bound siRNA duplexes, thus preventing the retention of the guide strand from interaction with R2D2, a key component for the assembly of the RNA-induced silencing complex.