Autoregulatory systems controlling translation factor expression: Thermostat-like control of translational accuracy

Abstract

In both prokaryotes and eukaryotes, the expression of a large number of genes is controlled by negative feedback, in some cases operating at the level of translation of the mRNA transcript. Of particular interest are those cases where the proteins concerned have cell-wide function in recognizing a particular codon or RNA sequence. Examples include the bacterial translation termination release factor RF2, initiation factor IF3, and eukaryote poly(A) binding protein. The regulatory loops that control their synthesis establish a negative feedback control mechanism based upon that protein's RNA sequence recognition function in translation (for example, stop codon recognition) without compromising the accurate recognition of that codon, or sequence during general, cell-wide translation. Here, the bacterial release factor RF2 and initiation factor IF3 negative feedback loops are reviewed and compared with similar negative feedback loops that regulate the levels of the eukaryote release factor, eRF1, established artificially by mutation. The control properties of such negative feedback loops are discussed as well as their evolution. The role of negative feedback to control translation factor expression is considered in the context of a growing body of evidence that both IF3 and RF2 can play a role in stimulating stalled ribosomes to abandon translation in response to amino acid starvation. Here, we make the case that negative feedback control serves primarily to limit the overexpression of these translation factors, preventing the loss of fitness resulting from an unregulated increase in the frequency of ribosome drop-off.

Plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified IgG antibodies from malaria-resistant mice

“…Modified amino acid bioavailability during Plasmodium infection causes dysregulation of l-arginine metabolism (Omodeo-Sale et al 2010) and modulates NO inflammatory responses (Yeo et al 2007). Moreover, accurate control of IF3 expression limits the premature or inappropriate abandoning of translation that would otherwise compromise cell fitness (reviewed in Betney et al 2010). Thus, blocking the functionality of this essential factor by the host immune response remains to be explored to address the immunoprotective role of this newly identified antigen.…”

Both the autophagy and proteasomal pathways facilitate the Ubp3p-dependent depletion of a subset of translation and RNA turnover factors during nitrogen starvation in Saccharomyces cerevisiae

“…Finally, we explored the effect of autophagy on translation termination during nitrogen starvation. The efficiency of translation termination is determined by the relative abundance of release factors, aminoacyl tRNAs, and terminating ribosomes (Betney et al 2010). During nitrogen starvation, the steady-state levels of both ribosomes and eRF3 are reduced.…”

Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1)

“…Autoregulation of the synthesis of translation factors is often observed (17). Initiation of IF3 translation begins with an AUU codon that is an important component of a negative feedback regulatory loop.…”