Abstract
The ability to respond to metabolic or environmental changes is an essential feature in all cells and involves both transcriptional and translational regulators that adjust the metabolic activity to fluctuating conditions. While transcriptional regulation has been studied in detail, the important role of the ribosome as an additional player in regulating gene expression is only beginning to emerge. Ribosome-interacting proteins are central to this translational regulation and include universally conserved ribosome interacting proteins, such as the ATPase YchF (Ola1 in eukaryotes). In both eukaryotes and bacteria, the cellular concentrations of YchF/Ola1 determine the ability to cope with different stress conditions and are linked to several pathologies in humans. The available data indicate that YchF/Ola1 regulates the stress response via controlling non-canonical translation initiation and via protein degradation. Although the molecular mechanisms appear to be different between bacteria and eukaryotes, increased non-canonical translation initiation is a common consequence of YchF/Ola1 regulated translational control in E. coli and H. sapiens. In this review, we summarize recent insights into the role of the universally conserved ATPase YchF/Ola1 in adapting translation to unfavourable conditions.
Highlights
All cells, in particular unicellular organisms, are permanently challenged by rapid environmental changes and depend on sophisticated mechanisms for adjusting their metabolic activity to external cues
Examples are the ribosome modulation factor (RMF) and the hibernation-promoting factor (HPF), which are produced during the stationary phase in Escherichia coli [7,8,9]
The presence of an uncharged tRNA in the A-site of the ribosome serves as a signal for recruiting the GTP-pyrophosphokinase RelA to the ribosome
Summary
In particular unicellular organisms, are permanently challenged by rapid environmental changes and depend on sophisticated mechanisms for adjusting their metabolic activity to external cues. A major hallmark of these adjustments are transcriptional regulators, such as two-component systems [1,2] or various sigma factors [3] that rapidly adapt gene expression in response to, e.g., temperature shifts, pH shifts or nutrient limitation In addition to these well-studied transcriptional responses, bacteria adjust their metabolism by modifying the translational activity of the ribosome [4,5,6]. This rapidly reversible inactivation of ribosomes is considered to prevent ribosomal damage while simultaneously reducing the production of damageprone translation products Another example for translational regulation is the so-called stringent response, which is initiated during nutrient limitation, e.g., shortage of amino acids [10,11].
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