Gene expression in eukaryotes is regulated at multiple levels. Whereas the mechanisms that regulate the early and late steps in this cascade – transcription and post-translational modifications – have been studied in great detail, much less is known about the intervening steps. In particular, the regulatory processes controlling the fate of mRNAs in the cytosol (mRNA stability, subcellular localization, translation) are still poorly understood. In the last few years, it has become apparent that mRNA metabolism is heavily and dynamically regulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs).
Hundreds of RBPs and miRNAs are present in metazoan organisms, rivaling in number other classes of regulatory molecules such as transcription factors and kinases. Moreover, both RBPs and miRNAs appear to have on average between dozens and hundreds of targets. Consequently, it is estimated that at least two thirds of all human genes are regulated at the mRNA level by RBPs and miRNAs (Bartel, 2009). miRNAs preferentially regulate transcription factors and the RBPs frequently regulate their own mRNAs, suggesting that RBPs and miRNAs might be used to modulate coordinately almost every aspect of a cell's life. Aberrations in RBP or miRNA expression can readily lead to human diseases, further underscoring the importance of these regulatory molecules for proper development and homeostasis. As the significance of RBPs and miRNAs in the regulation of gene expression is increasingly recognized, the interest in characterizing their mode of action, the targets that they regulate, and how RBP and miRNA systems interact with each other is rising.
In this project we propose to use a multi-disciplinary approach to construct a comprehensive view of the involvement of RBPs and miRNAs in the regulation of a physiologically relevant process: germ cell apoptosis in the invertebrate nematode C. elegans.