The Stringent Response—21 Years On

Abstract

During normal growth, bacteria synthesize no more ribosomes than can be engaged with high efficiency in protein synthesis (1). The molecular mechanism maintaining this fine balance is clearly of crucial importance in determining the growth characteristics of the cell. The first inkling that the synthesis of an essential component of the ribosome, the ribosomal RNA, might be directly coupled to protein synthesis was provided in 1952 by Sands and Roberts (2). They observed that when a particular bacterial strain was deprived of a required amino acid, not only did protein synthesis stop but also the net synthesis of RNA was substantially reduced. This phenomenon, subsequently christened the “;stringent response,” has recently been the subject of several excellent reviews (1,3,4). In this chapter, I argue that the stringent response is an extreme manifestation of the normal processes of the gross control of RNA synthesis in the bacterial cell. I further suggest that a major mode of effecting the selective coupling of stable RNA species to protein synthesis is mediated by EF-TuTs, a protein synthesis elongation factor, and ppGpp, a metabolic product of the ribosome (5).