Functional analysis of RNP complexes in eukaryotic mRNA translation

Abstract

Protein synthesis is a complex and poorly understood process that requires the concerted activity of ribosomes and a plethora of trans-acting protein factors. This dissertation used proteomic, biochemical, and functional analysis to conclude that the Saccharomyces cerevisiae ribosome contains the protein Asc1p. One of Asc1p’s functions is to represses the synthesis of a subset of proteins in yeast. At elevated temperatures Asc1p is required for ribosome biogenesis. This dissertation also identified trans-acting proteins that activate the cap-independent translation of the ornithine decarboxylase mRNA. One of these proteins, ZNF9, is mutated in type-2 myotonic dystrophy. Future studies aimed at discovering the regulatory targets of ZNF9 may lead to an improved understanding of this disease’s pathogenesis.