Silence Blog

Dicer-1 rules!

It has been more than a decade since Dicer was identified as the siRNA and miRNA-generating enzyme. Dicer proteins exist in nearly all eukaryotes and are well know for their ability to convert long, double-stranded RNA, or miRNA precursors (pre-miRNAs) into 21-23 nt long duplexes. Therefore, Dicer has been dubbed a ‘molecular ruler.’

In Drosophila melanogaster there are two Dicer proteins. Dicer-2—along with its partner R2D2—processes long, double-stranded RNA; whereas Dicer-1 cleaves miRNA precursors—stem-loop RNAs ∼70 nt long. What restricts Dicer-1 to processes primarily pre-miRNA into and not long double-stranded RNA?

Using classical biochemistry, Tsutsumi et al. (doi:10.1038/nsmb.2125) now show that fly Dicer-1 recognizes the single-stranded terminal loop of pre-miRNA through the Dicer-1 helicase domain, sensing terminal loop size and measuring the distance from the 3ʹ overhang to the terminal loop. Stem-loop RNAs whose stems are longer than those of canonical pre-miRNAs are poor Dicer-1 substrates. Consequently, fly Dicer-1 fails to process long, double-stranded RNAs. By measuring the distance from the 3´ end to the loop, Dicer-1 indeed earns the title ‘Molecular ruler.’ 

Carlos Fabián Flores-Jasso, Ph.D.

Posted by Elizabeth Bal at 17:13    Comments (0)