title: Ribosomal protein L3 mutants alter translational fidelity and promote rapid loss of the yeast killer virus.
abstract: Programmed -1 ribosomal frameshifting is utilized by a number of RNA viruses as a means of ensuring the correct ratio of viral structural to enzymatic proteins available for viral particle assembly. Altering frameshifting efficiencies upsets this ratio, interfering with virus propagation. We have previously demonstrated that compounds that alter the kinetics of the peptidyl-transfer reaction affect programmed -1 ribosomal frameshift efficiencies and interfere with viral propagation in yeast. Here, the use of a genetic approach lends further support to the hypothesis that alterations affecting the ribosome's peptidyltransferase activity lead to changes in frameshifting efficiency and virus loss. Mutations in the RPL3 gene, which encodes a ribosomal protein located at the peptidyltransferase center, promote approximately three- to fourfold increases in programmed -1 ribosomal frameshift efficiencies and loss of the M1 killer virus of yeast. The mak8-1 allele of RPL3 contains two adjacent missense mutations which are predicted to structurally alter the Mak8-1p. Furthermore, a second allele that encodes the N-terminal 100 amino acids of L3 (called L3Delta) exerts a trans-dominant effect on programmed -1 ribosomal frameshifting and killer virus maintenance. Taken together, these results support the hypothesis that alterations in the peptidyltransferase center affect programmed -1 ribosomal frameshifting.
authors.affiliation: The Cancer Institute of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Peltz
authors.forename: A B
authors.initials: AB
authors.lastname: Hammell
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.forename: J
authors.initials: J
authors.lastname: Yasenchak
authors.forename: L
authors.initials: L
authors.lastname: Puljanowski
authors.forename: J D
authors.initials: JD
authors.lastname: Dinman
mesh_terms: D000483:Alleles; D005095:Exoribonucleases / Q000235:genetics; D063326:Exosome Multienzyme Ribonuclease Complex; D016368:Frameshift Mutation; D015870:Gene Expression; D009154:Mutation; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D010957:Plasmids; D012328:RNA Viruses / Q000235:genetics; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000821:virology*; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
chemical_list: D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; C111978:SKI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D010458:Peptidyl Transferases; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex