TY - JOUR

T1 - Modulation of efficiency of translation termination in Saccharomyces cerevisiae

T2 - Turning nonsense into sense

AU - Nizhnikov, A.A.

AU - Antonets, K.S.

AU - Inge-Vechtomov, S.G.

AU - Derkatch, I.L.

PY - 2014

Y1 - 2014

N2 - Nonsense suppression is a readthrough of premature termination codons. It typically occurs either due to the recognition of stop codons by tRNAs with mutant anticodons, or due to a decrease in the fidelity of translation termination. In the latter case, suppressors usually promote the readthrough of different types of nonsense codons and are thus called omnipotent nonsense suppressors. Omnipotent nonsense suppressors were identified in yeast Saccharomyces cerevisiae in 1960s, and most of subsequent studies were performed in this model organism. Initially, omnipotent suppressors were localized by genetic analysis to different protein- and RNA-encoding genes, mostly the components of translational machinery. Later, nonsense suppression was found to be caused not only by genomic mutations, but also by epigenetic elements, prions. Prions are self-perpetuating protein conformations usually manifested by infectious protein aggregates. Modulation of translational accuracy by prions reflects changes in the activity of their structural proteins involved in different aspects of protein synthesis. Overall, nonsense suppression can be seen as a "phenotypic mirror" of events affecting the accuracy of the translational machine. However, the range of proteins participating in the modulation of translation termination fidelity is not fully elucidated. Recently, the list has been expanded significantly by findings that revealed a number of weak genetic and epigenetic nonsense suppressors, the effect of which can be detected only in specific genetic backgrounds. This review summarizes the data on the nonsense suppressors decreasing the fidelity of translation termination in S. cerevisiae, and discusses the functional significance of the modulation of translational accuracy.

AB - Nonsense suppression is a readthrough of premature termination codons. It typically occurs either due to the recognition of stop codons by tRNAs with mutant anticodons, or due to a decrease in the fidelity of translation termination. In the latter case, suppressors usually promote the readthrough of different types of nonsense codons and are thus called omnipotent nonsense suppressors. Omnipotent nonsense suppressors were identified in yeast Saccharomyces cerevisiae in 1960s, and most of subsequent studies were performed in this model organism. Initially, omnipotent suppressors were localized by genetic analysis to different protein- and RNA-encoding genes, mostly the components of translational machinery. Later, nonsense suppression was found to be caused not only by genomic mutations, but also by epigenetic elements, prions. Prions are self-perpetuating protein conformations usually manifested by infectious protein aggregates. Modulation of translational accuracy by prions reflects changes in the activity of their structural proteins involved in different aspects of protein synthesis. Overall, nonsense suppression can be seen as a "phenotypic mirror" of events affecting the accuracy of the translational machine. However, the range of proteins participating in the modulation of translation termination fidelity is not fully elucidated. Recently, the list has been expanded significantly by findings that revealed a number of weak genetic and epigenetic nonsense suppressors, the effect of which can be detected only in specific genetic backgrounds. This review summarizes the data on the nonsense suppressors decreasing the fidelity of translation termination in S. cerevisiae, and discusses the functional significance of the modulation of translational accuracy.

KW - prion

KW - amyloid

KW - yeast

KW - nonsense suppression

KW - translation

KW - SUP35

KW - SUP45

KW - ribosome

KW - translation termination

KW - YEAST RIBOSOMAL-PROTEIN

KW - MESSENGER-RNA TURNOVER

KW - TRANSCRIPTIONAL REGULATOR SFP1

KW - PRION-LIKE DETERMINANT

KW - CHAIN RELEASE FACTOR

KW - DE-NOVO APPEARANCE

KW - STOP CODON

KW - OMNIPOTENT SUPPRESSORS

KW - GENETIC-CODE

KW - FACTOR ERF3

U2 - 10.4161/pri.29851

DO - 10.4161/pri.29851

M3 - Review article

C2 - 25486049

VL - 8

SP - 247

EP - 260

JO - Prion

JF - Prion

SN - 1933-6896

IS - 3

ER -