Cell cycle control (and more) by programmed −1 ribosomal frameshifting: implications for disease and therapeutics

摘要

Like most basic molecular mechanisms, programmed –1 ribosomal frameshifting (>−1 PRF) was first identified in viruses. Early observations that global dysregulation of >−1 PRF had deleterious effects on yeast cell growth suggested that >−1 PRF may be used to control cellular gene expression, and the cell cycle in particular. Collection of sufficient numbers of viral >−1 PRF signals coupled with advances in computer sciences enabled 2 complementary computational approaches to identify >−1 PRF signals in free living organisms. The unexpected observation that almost all >−1 PRF events on eukaryotic mRNAs direct ribosomes to premature termination codons engendered the hypothesis that >−1 PRF signals post-transcriptionally regulate gene expression by functioning as mRNA destabilizing elements. Emerging research suggests that some human diseases are associated with global defects in >−1 PRF. The recent discovery of >−1 PRF signal-specific trans-acting regulators may provide insight into novel therapeutic strategies aimed at treating diseases caused by changes in gene expression patterns.