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Elucidation of the evolution of post-transcriptional regulation by characterizing the cnidarian microRNA pathway

Periodic Reporting for period 4 - CNIDARIAMICRORNA (Elucidation of the evolution of post-transcriptional regulation by characterizing the cnidarian microRNA pathway)

Reporting period: 2019-11-01 to 2020-04-30

In this project we are interested in elucidating the way microRNAs function in sea anemones. microRNAs are small molecules that bind to the products of genes (called messenger RNA) and control their stability and fate. We know today that the differences between species do not only depend on the identity or number of genes, but also on the differences in the expression levels of a gene (how much product is made from a given gene). Sea anemones are marine animals that are cousins of jellyfish and corals and together they represent a group that separated from the rest of the animals about 600 million years ago. Despite their apparent primitive and simple state, these gelatinous animals have a complex gene repertoire that is similar to that of humans and other higher animals. Thus, we suspect that the vast difference in complexity between sea anemones and higher animals might result from regulatory features such as microRNAs. Indeed, in our research we found out that microRNAs act differently in sea anemones compared to higher animals and surprisingly their mode of action in sea anemones resembles that of plant microRNAs. Our project is aimed at characterizing in detail the mode of action of microRNAs and the way they are produced in sea anemones in order to understand their evolutionary origin and in order to assess the role of the microRNA system in influencing the striking difference in complexity between different organisms. Our project can also unravel how microRNAs functioned in ancient animals before the separation of sea anemones and other animals. We strongly believe that society will benefit from understanding the ancient origin of animals and the reasons behind the differences in animal complexity across evolutionary history, as this can tell us about what makes us different from primitive animals and what are the factors behind our increased complexity.
"We have recruited several talented scientists to this project in its five years and run a team of PhD students, postdocs, a technician and a sea anemone care taker to fulfill the goals of the project. In addition, we have assembled and installed a microinjection setup that enables us to manipulate genes in sea anemones. We have used this setup to attenuate genes that are involved in the microRNA system in the sea anemone (for example Dcier, which is an enzyme that produces microRNAs in their mature form) to see whether the manipulation of this system has any effect on the sea anemone. Strikingly, we have seen noticeable effects clearly indicating that microRNAs are essential molecules in sea anemones. One process which is clearly affected is the development of the animal, as animals genetically manipulated so they cannot produce microRNAs fail to develop into mature animals (see accompanying figure). Further, we have found that some proteins that are important for microRNA action in higher animals but are missing from plants are also found in sea anemones, whereas other proteins that were considered ""plant specific"" are also involved in the microRNA system of sea anemones. This suggests that the microRNA system in sea anemones might be at a ‘mixed’ state between plants and animals and possibly serve as an evolutionary transition state between the two systems. This is a significant step forward in our understanding of the evolution of genetic regulation in early animals that lived hundreds of millions of years ago."
Our results in thia project show two important things that can be considered a leap forward in our understanding of gene regulation in animals:
1. microRNAs play an important role in the physiology of ‘lower animals’ such as sea anemones and not only in higher animals
2. The state of the microRNA-based regulation system in sea anemones seems to be a possible “evolutionary intermediate” between the system of higher animals and plants.
We believe that such results have an impact on the way we think about the evolution of gene regulation as biologists. Further, as they have implications on the evolutionary history of animals we believe that society benefits from this research as many people even outside of the scientific community are fascinated by nature and especially by animals. At the end of the day, humans are interested in their origin and their ancient roots and our research implicates how ancient animals from the lineage that led to us humans functioned on the molecular and genomic levels hundreds of millions of years ago.
The effect of Dicer inhibition in Nematostella vectensis