You'd Prefer An Argonaute

A distinct class of small RNAs arises from pre-miRNA–proximal regions in a simple chordate

Weiyang Shi, David Hendrix, Mike Levine & Benjamin Haley

Nature Structural & Molecular Biology 16 (2): 183-189, February 2009.
doi:10.1038/nsmb.1536

This week’s forthright summary and analysis comes from Anna Drinnenberg:

Using high-through-put sequencing the authors of this paper describe the identification of a new class of small RNAs encoded in the Ciona intestinalis genome that arise from positions adjacent to pre-miRNAs in predicted hairpins. In total, these small RNAs are in very low abundance in the sequencing libraries (~1500 reads compared to more than 1 million reads for mature miRNAs) and have about half the number of reads compared to miRNA* sequences. They state that half of the miRNA genes in Ciona give rise to such miRNA-offset RNAs. In three examples shown, the total number of reads mapping to these offset RNAs add up to about the total number of reads of miRNA-offset RNAs in all libraries together which raises the question whether a significant amount of miRNA-offset RNA is generated from the other miRNA genes that were not shown. They suggest a model in which a sequential or parallel processing step by Drosha could explain the biogenesis of these RNAs. Based on their data in which complementary sequences to miRNA-offset RNAs are detectable in only a few cases at low abundance, and considering the highly unpaired structure of shown miRNA-offset RNA duplexes, it seems unlikely that an RNaseIII enzyme is involved in processing. The experimental procedure that included expression of a Drosophila miRNA hairpin to induce miRNA-offset RNA production in the Ciona tadpole is a very interesting and creative follow-up to their sequencing results, however, the assumption that these RNAs constitute a new class of small RNA and aren’t just by-products of (exonucleolytic degradation) miRNA processing is not convincing.