The human Dicer helicase domain is capable of ATP hydrolysis and single-stranded nucleic acid binding.

Background: Vertebrates have one Dicer ortholog that generates both microRNAs (miRNAs) and small interfering RNAs (siRNAs), in contrast to the multiple Dicer-like proteins found in flies and plants. Here, we focus on the functions of the human Dicer (hDicer) helicase domain. The helicase domain of hDicer is known to recognize pre-miRNA substrates through interactions with their apical loop regions. Besides interacting with canonical substrates, the hDicer helicase domain has also been suggested to bind many different cellular RNAs; however, a comprehensive study of the biochemical activities and substrate specificity of the hDicer helicase domain towards different nucleic acids has yet to be undertaken.

Results: Here, we reveal that full-length hDicer, through its helicase domain, hydrolyzes ATP. The ATPase activity of hDicer can only be observed under low-turnover conditions. To the best of our knowledge, this is the first time this activity has been reported for vertebrate Dicers. We also show that the hDicer helicase domain binds single- but not double-stranded RNAs and DNAs and that this binding activity presumably is not nucleotide-dependent. Moreover, the hDicer helicase domain may influence the structure of the RNA to which it binds.

Conclusions: Preservation of ATPase activity by hDicer suggests that this enzyme performs many more functions in the cell than is currently assumed. Our findings open new avenues for future studies aimed at defining the cellular activities of hDicer that may be associated with these newly described biochemical properties: ATP hydrolysis and single-stranded nucleic acid binding activities.