miRNA expression profiling of ciliogenesis
Final Report Abstract
The cilium, also known as the "cell antenna”, is a slender protuberance extending from the surface of nearly every cell in the mammalian body. Cilia can be either motile or immotile, the latter being referred to as primary cilia. The primary cilium was first identified more than a century ago, however, in contrast to motile cilia, the importance of the primary cilia has gone unnoticed for several years. In the last decade, mutations that impair cilia formation or its signaling activity have been shown to have severe consequences for development and for postnatal tissue physiology. Several disorders (the ciliopathies) have found to be caused by cilia-related defects. The ciliopathies encompass a variety of apparently distinct disorders depending upon the organs most severely affected. With this project we aimed to identify key processes involved in primary cilia growth and maintenance and to investigate on the involvement of microRNAs in primary cilia development. MicroRNAs (miRNAs) are small non-coding RNAs of 20-30 nucleotides in length, present ubiquitously in animals, plants, and viruses. MiRNAs can control the expression level of specific messanger RNAs, and thus, protein amount. Using a genetically engineered human cell line, we screened for miRNAs potentially involved in primary cilia development. We identified a number of miRNAs that, in our system, were negatively or positively regulating cilia number and/or length as well as 200 mRNAs potentially regulated by our candidate miRNAs. While more functional work will be required to understand how these mRNAs may regulate ciliogenesis, our study suggests an important role for miRNAs in cilia development and function.
Publications
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Modeling human disease in humans: the ciliopathies. Cell 2011 Sep 30;147(1):70-9
Novarino G, Akizu N, Gleeson JG
