The main goal of this project is to understand how non-coding RNA molecules help the embryos of animals establish an anterior end (or head) and a posterior end (or tail) during development. Recently, non-coding RNA molecules (called non-coding because they do not code for proteins) have been implicated in this developmental process. This project aims to discover how a non-coding RNA called 7SK helps control anterior development. The results will be important for the fundamental understanding of how animals develop, and may find future applications in nanotechnology. The project will involve the training of junior scientists at the post-doctoral, graduate and undergraduate levels.
Long non-coding RNAs have emerged as critical regulators of gene expression, but how they function is still a mystery. Here, an unusual non-coding RNA polymerase III transcript called 7SK RNA and its key regulator, the Bin3 RNA methyltransferase (called MePCE in mammals), will be studied. 7SK RNA is conserved from yeast to humans and plays critical roles in both transcription and translation. Bin3 seems to have co-evolved with 7SK RNA and methylates its 5'-y-phosphate. Bin3 was discovered in Drosophila melanogaster where it is required for proper anterior-posterior embryo development. The mechanism is not known. The proposed experiments will: (1) test the model that methylation of 7SK RNA by Bin3 is important for Bicoid-dependent repression of caudal mRNA translation; (2) determine the step in translation at which the Bin3-7SK-RNA complex exerts it regulatory effect; (3) determine whether Bin3 targets other non-coding RNAs for 5'-y-methylation and whether it represses translation of other mRNAs. The results will help in determining exactly how embryo development is controlled by non-coding RNAs in Drosophila and provide a model for how the Bin3-7SK-RNA complex works in other eukaryotic organisms. The integrated approach will combine genetics, biochemistry, bioinformatics and computational prediction.
