? Faithful maintenance of translational reading frame is a basic requirement for translation of genetic information from genes into proteins. Exceptions to this rule have been characterized mostly in RNA viruses, where specific cis-acting mRNA signals induce elongating ribosomes to shift reading frame. Given that many basic biological regulatory mechanisms have been first in viral systems, we hypothesize that programmed ribosomal frameshifting is utilized to regulate the expression of a significant subset of cellular genes as well. If so, this would represent a significant shift in our view of protein translation, and may have significant impact on our understanding of many of the underlying causes of birth defects, cancer and aging. Preliminary studies are presented supporting this hypothesis. These include bioinformatic, RNA-blot, and a preliminary set of DNA microarray analyses. The proposed studies will expand upon a DNA microarray approach to identify cellular mRNAs that are regulated by programmed -1 ribosomal frameshifting (-1 PRF). The overall strategy will be to identify cellular mRNAs that are specifically stabilized under conditions where -1 PRF is inhibited, and conversely, those that are destabilized when -1 PRF is stimulated. The data generated from these experiments will be compared with one another and with our database of consensus -1 PRF signal containing genes in order to identify the best candidates for further characterization with regard to the role that -1 PRF may play in theregulation of their expression. ? ?
