Specific effects of ribosome-tethered molecular chaperones on programmed -1 ribosomal frameshifting.
The ribosome-associated molecular chaperone complexes RAC (Ssz1p/Zuo1p) and Ssb1p/Ssb2p expose a link between protein folding and translation. Disruption of the conserved nascent peptide-associated complex results in cell growth and translation fidelity defects. To better understand the consequences of deletion of either RAC or Ssb1p/2p, experiments relating to cell growth and programmed ribosomal frameshifting (PRF) were assayed. Genetic analyses revealed that deletion of Ssb1p/Ssb2p or of Ssz1p/Zuo1p resulted in specific inhibition of -1 PRF and defects in Killer virus maintenance, while no effects were observed on +1 PRF. These factors may provide a new set of targets to exploit against viruses that use -1 PRF. Quantitative measurements of growth profiles of isogenic wild-type and mutant cells showed that translational inhibitors exacerbate underlying growth defects in these mutants. Previous studies have identified -1 PRF signals in yeast chromosomal genes and have demonstrated an inverse relationship between -1 PRF efficiency and mRNA stability. Analysis of published DNA microarray experiments reveals conditions under which Ssb1, Ssb2, Ssz1, and Zuo1 transcript levels are regulated independently of those of genes encoding ribosomal proteins. Thus, the findings presented here suggest that these trans-acting factors could be used by cells to posttranscriptionally regulate gene expression through -1 PRF.
Muldoon-Jacobs
Kristi L
KL
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Dinman
Jonathan D
JD
D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics*; D018965:Frameshifting, Ribosomal / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000502:physiology; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D012097:Repressor Proteins; C095192:SSB1 protein, S cerevisiae; C424445:SSZ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C077019:ZUO1 protein, S cerevisiae