18 research outputs found
Mechanism of activation of methyltransferases involved in translation by the Trm112 âhubâ protein
Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases
Decoding accuracy in eRF1 mutants and its correlation with pleiotropic quantitative traits in yeast
Translation termination in eukaryotes typically requires the decoding of one of three stop codons UAA, UAG or UGA by the eukaryotic release factor eRF1. The molecular mechanisms that allow eRF1 to decode either A or G in the second nucleotide, but to exclude UGG as a stop codon, are currently not well understood. Several models of stop codon recognition have been developed on the basis of evidence from mutagenesis studies, as well as studies on the evolutionary sequence conservation of eRF1. We show here that point mutants of Saccharomyces cerevisiae eRF1 display significant variability in their stop codon read-through phenotypes depending on the background genotype of the strain used, and that evolutionary conservation of amino acids in eRF1 is only a poor indicator of the functional importance of individual residues in translation termination. We further show that many phenotypes associated with eRF1 mutants are quantitatively unlinked with translation termination defects, suggesting that the evolutionary history of eRF1 was shaped by a complex set of molecular functions in addition to translation termination. We reassess current models of stop-codon recognition by eRF1 in the light of these new data
Why Opt-Out Defaults Diminish Living Organ Donations
Opt-out defaults can motivate people towards more prosocial behavior and many countries have adopted opt-out defaults to increase deceased organ donation, energy conservation, or childhood vaccination. Prior studies show that opt-out defaults are powerful for increasing a specific cooperative behavior (e.g., deceased organ donation). However, little is known about how they may spillover to influence related cooperative behaviors (e.g., living organ donation) and how they may interact with mechanisms known to support human cooperation (e.g., inclusive fitness and reputation building). The present research addresses these gaps by investigating how an opt-out default policy for deceased organ donation influences the supply of living organs and how exposure to different default policies (opt-in or opt-out) alters perceptions of trust in others, inclusive fitness, and reputation building considerations. Across three studies, we show that the cooperative opt-out defaults for deceased organ donations have negative spillover-effects on living donations, which are larger for people with stronger pure altruistic tendencies. We show that this negative spillover effect is due to enhanced trust that organ supply approaches demand under opt-out. We further show that this interpretative change in organ supply leads to reduced living organ donations by (i) undermining the reputation-building effect of living organ donation and (ii) making people less willing to donate a living organ to recipients low in genetic relatedness and emotional closeness. The studyâs findings have important implications for policymakers who aim to increase human cooperation by setting cooperative defaults