CONTROL OF CELL GROWTH

University Of Washington, Seattle WA

Investigators

Abstract

In translating the genetic code, ribosomes normally move along the messenger RNA reading one codon at a time. Ribosomes maintain a reading frame by moving in three-base steps. However, alternative forms of movement, can produce single-base changes in reading frame either backward (to the left, toward the 5' end of the message) or forward (to the right, toward the 3' end of the message). Such programmed changes producing two different essential translation products, have been found particularly in the translation of viral RNAs, but also occasionally in chromosomal genes. This proposal focuses on three categories of unconventional ribosome movement. First is the stimulation of both leftward and rightward frameshifting at so-called "hungry" codons where the ribosome stalls due to a limiting supply of cognate aminoacyl-tRNA. Second is the stimulation of frameshifting in stationary phase or during carbon/energy source downshift which is independent of frameshifting at "hungry" codons. Third, is the recently discovered phenomenon of ribosome leaping at hungry codons. In this case, the ribosome-peptidyl-tRNA complex skips a long stretch of mRNA and then resumes translation elongation at a downstream site. This is especially interesting because of the possibility that pt-tRNA can remain stably bound in the ribosomal P site without directly engaging mRNA during the process of ribosome movement (by whatever mechanism) to the so-called landing site at which elongation resumes. Because starvation conditions and the occurrence of a hungry codon may be frequent in nature, these phenomena are important to an understanding of translation and its control.