title: P-site tRNA is a crucial initiator of ribosomal frameshifting.
abstract: The expression of some genes requires a high proportion of ribosomes to shift at a specific site into one of the two alternative frames. This utilized frameshifting provides a unique tool for studying reading frame control. Peptidyl-tRNA slippage has been invoked to explain many cases of programmed frameshifting. The present work extends this to other cases. When the A-site is unoccupied, the P-site tRNA can be repositioned forward with respect to mRNA (although repositioning in the minus direction is also possible). A kinetic model is presented for the influence of both, the cognate tRNAs competing for overlapping codons in A-site, and the stabilities of P-site tRNA:mRNA complexes in the initial and new frames. When the A-site is occupied, the P-site tRNA can be repositioned backward. Whether frameshifting will happen depends on the ability of the A-site tRNA to subsequently be repositioned to maintain physical proximity of the tRNAs. This model offers an alternative explanation to previously published mechanisms of programmed frameshifting, such as out-of-frame tRNA binding, and a different perspective on simultaneous tandem tRNA slippage.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330, USA.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Baranov
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Gesteland
authors.forename: John F
authors.initials: JF
authors.lastname: Atkins
mesh_terms: D000818:Animals; D000926:Anticodon / Q000378:metabolism; D003062:Codon / Q000378:metabolism; D018965:Frameshifting, Ribosomal / Q000502:physiology*; D006801:Humans; D012343:RNA, Transfer / Q000378:metabolism*; D016364:Reading Frames / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000926:Anticodon; D003062:Codon; D012343:RNA, Transfer