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The Impact of the Stringent Response on TRAFAC GTPases and Prokaryotic Ribosome Assembly

The Florey Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1313;
Received: 30 September 2019 / Revised: 17 October 2019 / Accepted: 23 October 2019 / Published: 24 October 2019
(This article belongs to the Special Issue Ribosome Function and Dynamics)
Many facets of ribosome biogenesis and function, including ribosomal RNA (rRNA) transcription, 70S assembly and protein translation, are negatively impacted upon induction of a nutrient stress-sensing signalling pathway termed the stringent response. This stress response is mediated by the alarmones guanosine tetra- and penta-phosphate ((p)ppGpp), the accumulation of which leads to a massive cellular response that slows growth and aids survival. The 70S bacterial ribosome is an intricate structure, with assembly both complex and highly modular. Presiding over the assembly process is a group of P-loop GTPases within the TRAFAC (Translation Factor Association) superclass that are crucial for correct positioning of both early and late stage ribosomal proteins (r-proteins) onto the rRNA. Often described as ‘molecular switches’, members of this GTPase superfamily readily bind and hydrolyse GTP to GDP in a cyclic manner that alters the propensity of the GTPase to carry out a function. TRAFAC GTPases are considered to act as checkpoints to ribosome assembly, involved in binding to immature sections in the GTP-bound state, preventing further r-protein association until maturation is complete. Here we review our current understanding of the impact of the stringent response and (p)ppGpp production on ribosome maturation in prokaryotic cells, focusing on the inhibition of (p)ppGpp on GTPase-mediated subunit assembly, but also touching upon the inhibition of rRNA transcription and protein translation. View Full-Text
Keywords: ribosome; GTPase; stringent response; ppGpp; assembly cofactors; TRAFAC ribosome; GTPase; stringent response; ppGpp; assembly cofactors; TRAFAC
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Bennison, D.J.; Irving, S.E.; Corrigan, R.M. The Impact of the Stringent Response on TRAFAC GTPases and Prokaryotic Ribosome Assembly. Cells 2019, 8, 1313.

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