Selective translation during stress in Escherichia coli

Abstract

The bacterial stress response, a strategy to cope with environmental changes, is generally known to operate on the transcriptional level. Here, we discuss a novel paradigm for stress adaptation at the post-transcriptional level, based on the recent discovery of a stress-induced modified form of the translation machinery in Escherichia coli that is generated by MazF, the toxin component of the toxin-antitoxin (TA) module mazEF. Under stress, the induced endoribonuclease MazF removes the 3'-terminal 43 nucleotides of the 16S rRNA of ribosomes and, concomitantly, the 5'-untranslated regions (UTRs) of specific transcripts. This elegant mechanism enables selective translation due to the complementary effect of MazF on ribosomes and mRNAs, and also represents the first example of functional ribosome heterogeneity based on rRNA alteration.

Figure 1

Schematic depiction of the molecular mechanism that leads to selective translation during stress in Escherichia coli. Conditions that affect the expression of the mazEF module result in rapid degradation of the antitoxin MazE by the ClpAP protease [18,39,40]. Thereby the endoribonuclease MazF is released to exert its toxic effect. Besides degradation of the majority of transcripts [45], MazF removes the 5′-untranslated region (UTR) of specific mRNAs, thus rendering them leaderless. Moreover, it specifically removes the 3′-terminal 43 nucleotides of the 16S rRNA comprising the aSD sequence. As this sequence is of substantial importance for the formation of a translation initiation complex on canonical ribosome-binding sites [48,49], the generated specialized translation machinery selectively translate the leaderless mRNA regulon.

Figure 2

Site of MazF cleavage in the 16S rRNA of assembled and functionally active 70S ribosomes 5′ of nucleotide A1500. (a) The secondary structure of the 16S rRNA is shown. The decoding region and helices 44 and 45 that are indicated in light blue are enlarged in (b). The aSD sequence is indicated in green. The MazF recognition motive ACA is shown in red and the site of cleavage is indicated by an arrow.