Intrinsic Ribosome Destabilization Underlies Translation and Provides an Organism with a Strategy of Environmental Sensing

Nascent polypeptides can modulate the polypeptide elongation speed on the ribosome. Here, we show that nascent chains can even destabilize the translating Escherichia coli ribosome from within. This phenomenon, termed intrinsic ribosome destabilization (IRD), occurs in response to a special amino acid sequence of the nascent chain, without involving the release or the recycling factors. Typically, a consecutive array of acidic residues and those intermitted by alternating prolines induce IRD. The ribosomal protein bL31, which bridges the two subunits, counteracts IRD, such that only strong destabilizing sequences abort translation in living cells. We found that MgtL, the leader peptide of a Mg2+ transporter (MgtA), contains a translation-aborting sequence, which sensitizes the ribosome to a decline in Mg2+ concentration and thereby triggers the MgtA-upregulating genetic scheme. Translation proceeds at an inherent risk of ribosomal destabilization, and nascent chain-ribosome complexes can function as a Mg2+ sensor by harnessing IRD. [Display omitted] •Nascent chain sequences can abort translation by destabilizing the engaged ribosome•Consecutive and proline-intermitted acidic amino acids destabilize the 70S ribosome•Ribosomal protein bL31 counteracts the ribosome destabilization•A ribosome-nascent chain complex functions as a Mg2+ sensor Chadani et al. show that nascent chain handling of the translating ribosome includes ribosomal destabilization, resulting in translation abortion. This phenomenon, termed intrinsic ribosome destabilization (IRD), is induced by a class of amino acid sequences, typically containing multiple acidic residues. Living organisms harness IRD to sense Mg2+ concentrations.