Ribosome biogenesis is a major metabolic pathway, which is closely linked to the control of cell proliferation. In a complex pathway the ribosomal RNA (reran) precursors are covalently modified atman sites, processed by endow- and ego-nucleases and assembled with 80 ribosomal proteins into functional ribosomes. Over 200 factors have been implicated in this highly dynamic process in yeast, but the functions of most of these components remain unclear. Among these are 17 putative RNAhelicases (enzymes capable of ATP-dependent translocation and the unwinding of RNA duplexes), each of which is essential. Mature mRNAs have extensive secondary structure, which appears incompatible with ribosome assembly and their modification and processing requires base pairing with small nucleoli MRNAs (shorans). A need for RNA unwinding activities therefore seems clear, but the direct targets of the RNA helices are unknown. We propose to purify pre-ribosomal complexes at different stages of ribosome maturation from cells depleted of individual RNA helices. We will analyse the composition of these complexes and the ability of shorans and protein factors to associate with and dissociate from pre-ribosomes in the absence of the RNA helices will be determined. This will allow us to identify targets of the RNAhelicases and clarify their role in reran processing and ribosome synthesis. Ribosomal synthesis is an entirely new area of research for me. Nor have I any experience with yeast as a model organism, as I previously worked only with mammalian systems. The experience gained from this project would allow me to use the advantages of this powerful model system to understand the complexity of mammalian systems in my future research.
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