Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes

Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade

Make It Happen: Marketing Processes for Competitive Market Positioning of Firms in Transitional Economy

This paper presents some of the marketing processes, i.e. activities that firms in transitional economy can follow in the process of competitive market positioning. The main objective is to demonstrate that the practice of certain business processes, such as market orientation, market research, written marketing plans as a base for future business operations are correlated with creation of market positioning statements and thus increase the focus on market positioning in regards to competitors. This in addition, results in positive effects on profitability. Data are gathered through questionnaires and follow-up interviews. The results show that the analyzed processes have a positive outcome for firms in regards to competitive positioning. The creation of market positioning statement is found to be positively correlated with profitability. However, many of the firms in a transitional economy are slow in adapting to market changes, and have a selective approach to marketing activities. The most striking result is the more proactive approach of small and medium-sized enterprises in implementation of some of the marketing activities, like formal marketing planning and market research than large firms. Keywords: Domestic firms, Transitional economy, Market positioning, Market orientation, Formal marketing planning, Market researc