title: Cell cycle control (and more) by programmed -1 ribosomal frameshifting: implications for disease and therapeutics.
abstract: Abstract 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.
authors.affiliation: a Department of Cell Biology and Molecular Genetics ; University of Maryland ; College Park , MD USA.
authors.forename: Ashton T
authors.initials: AT
authors.lastname: Belew
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D030541:Databases, Genetic; D018965:Frameshifting, Ribosomal; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Ribosome; SCA26; aging; cancer; frameshifting; miRNA; pseudoknot; ribosomopathy; telomere; translation