The conserved theme of ribosome hibernation: from bacteria to chloroplasts of plants

Abstract

Cells are highly adaptive systems that respond and adapt to changing environmental conditions such as temperature fluctuations or altered nutrient availability. Such acclimation processes involve reprogramming of the cellular gene expression profile, tuning of protein synthesis, remodeling of metabolic pathways and morphological changes of the cell shape. Nutrient starvation can lead to limited energy supply and consequently, remodeling of protein synthesis is one of the key steps of regulation since the translation of the genetic code into functional polypeptides may consume up to 40% of a cell’s energy during proliferation. In eukaryotic cells, downregulation of protein synthesis during stress is mainly mediated by modification of the translation initiation factors. Prokaryotic cells suppress protein synthesis by the active formation of dimeric so-called ‘hibernating’ 100S ribosome complexes. Such a transition involves a number of proteins which are found in various forms in prokaryotes but also in chloroplasts of plants. Here, we review the current understanding of these hibernation factors and elaborate conserved principles which are shared between species.

Functional Analysis of PSRP1, the Chloroplast Homolog of a Cyanobacterial Ribosome Hibernation Factor

“…PSRP1 is a nucleus-encoded protein that was originally found in a proteomic analysis of chloroplast 30S ribosomal subunits, when it was assumed to be a bone fide ribosomal protein [5]. Subsequently, it became clear that PSRP1 belongs to a family of proteins called ribosome hibernation factors, the best studied example of which is Ribosome Associated Inhibitor 1 (Rai1) or pY in E. coli [6][7][8]. During stationary phase and at low temperatures, Rai1 binds the 30S ribosomal subunit, which induces a conformational change that favors the stable association of 30S and 50S subunits into inactive 70S ribosomes (reviewed in 7,8).…”

“…Subsequently, it became clear that PSRP1 belongs to a family of proteins called ribosome hibernation factors, the best studied example of which is Ribosome Associated Inhibitor 1 (Rai1) or pY in E. coli [6][7][8]. During stationary phase and at low temperatures, Rai1 binds the 30S ribosomal subunit, which induces a conformational change that favors the stable association of 30S and 50S subunits into inactive 70S ribosomes (reviewed in 7,8). Despite the strong conservation of Rai1-related factors in bacteria, bacterial mutants lacking them show only subtle changes in phenotype and their physiological roles remain unclear.…”

“…Proposed functions include global translational repression in response to stress, the protection of inactive ribosomes, and the rapid recovery of protein synthesis following stress-induced inhibition. The PSRP1 sequence places it in the "long Hibernation Promoting Factor" (l-HPF) subclass, members of which generally promote the formation of inactive 100S ribosome dimers [8]. Structural and biochemical data show, however, that PSRP1 binds and inactivates 70S ribosomes in a manner analogous to Rai1/pY [6][7][8][9][10][11].…”

“…The PSRP1 sequence places it in the "long Hibernation Promoting Factor" (l-HPF) subclass, members of which generally promote the formation of inactive 100S ribosome dimers [8]. Structural and biochemical data show, however, that PSRP1 binds and inactivates 70S ribosomes in a manner analogous to Rai1/pY [6][7][8][9][10][11]. PSRP1 binds the intersubunit space of chloroplast ribosomes, preventing access of tRNAs to the A and P sites [9,10].…”

Ribosome dimerization prevents loss of essential ribosomal proteins during quiescence

“…Most bacteria encode an HPF homolog, and mutants lacking HPF exhibit pleiotropic phenotypes, including decreased viability during extended stationary phase (12), increased antibiotic sensitivity (13), decreased virulence (14), and a reduction in protein synthesis and growth after nutrient limitation (15, 16). Ribosome dimerization may inhibit protein synthesis (17, 18) and bacteria lacking HPF exhibit increased polysomes, indicative of increased protein synthesis (19). However, phenotypes associated with HPF deletion may also be explained by ribosome instability as ribosomal RNA has been shown to be degraded in some mutants lacking HPF (15, 20, 21).…”