Evolutionary history of microRNA mode of action

It is proposed that MicroRNAs regulate the expression of many target genes, suggesting they act as master regulators of the genome. We found that the Cnidarian Nematostella vectensis expresses dozens of different microRNAs (contradicting previous claims linking the number of microRNA genes to a poorly-defined "organism complexity") and we saw that Cnidarian microRNAs frequently direct endonucleolytic cleavage of their RNA targets, similarly to what is observed in plants.

HFSP Career Development Award holder Hervé Seitz and colleagues
authored on Fri, 21 March 2014

MicroRNAs are small regulatory RNAs with thousands of predicted target genes in animals. The large diversity of microRNA targets suggests that every physiological process in animals is controlled by microRNAs at one step or another, leading to the notion that microRNAs have a central role in animal biology. In particular, several studies suggested that Deuterostomes (e.g., vertebrates, sea urchins) have more microRNA genes than Protostomes (e.g., flies, worms) and Protostomes would have more microRNA genes than non-bilateral animals (e.g., sea anemones, corals, jellyfish). Some studies proposed that the number of microRNAs correlates to organism complexity, but without providing a clear definition of "complexity".

Such resurgence of hierarchical classification of living species (with "higher" and "lower" species; these notions were already criticized by Darwin in 1837) may simply be caused by an observation bias (more microRNAs have been described in bilateral animals than in Cnidarians, but much more effort has been devoted to the search of microRNAs in bilateral animals than in Cnidarians). Indeed we discovered dozens of novel microRNAs in the sea anemone Nematostella vectensis, bringing the number of microRNAs in that Cnidarian close to the reported number of microRNAs in several bilateral animals.

Figure:  A female adult sea anemone (species Nematostella vectensis). "©CNRS Photothèque / Cyril Frésillon"

We also noticed that Nematostella microRNAs tend to be highly complementary to mRNAs, suggesting that they can direct endonucleolytic target cleavage (both in animals and in plants, a near-perfect complementarity between the microRNA and its target is necessary for that highly efficient repressive process). We could confirm experimentally that, indeed, microRNAs in Nematostella (but also in other Cnidarians) guide the cleavage of several target RNAs.

MicroRNAs in bilateral animals usually repress their targets by another mechanism, but plant microRNAs also frequently direct target cleavage. These observations suggest that endonucleolytic target cleavage is the ancestral mode of action of microRNAs both in plants and in animals.


Cnidarian microRNAs frequently regulate targets by cleavage. Moran, Y., Fredman, D., Praher, D., Li, X. Z., Wee, L. M., Rentzsch, F., Zamore, P. D., Technau, U., and Seitz, H. Genome Research (in press) doi: 10.1101/gr.162503.113.

Link to abstract

Link to Genome Research article