One of the early phases in assembly of a functional ribosome is the accurate processing of the ribosomal RNAs from a single precursor transcript. These reactions include placement of nucleotide modifications and cleavage steps that release the mature rRNAs. The long-term goal of this research is to examine how nucleotide modifications contributes to the assembly of the ribosome and subsequent levels of translation. Central to that goal is understanding the mechanism for accurate modification of the ribosomal RNA sequences.
The specific aims of this proposal are to develop an in vitro system for studying site-specific rRNA modification in vertebrates, and to study the RNA determinants contributing to the methylation activity using nucleotide analog interference mapping (NAIM). Studies on control of this initial phase of ribosome assembly are particularly germane to the issue of elevated protein synthesis in cancer cells characteristically exhibiting uncontrolled growth.
