Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control.
Cells employ many mechanisms to ensure quality control during protein biosynthesis. Here, we show that, during the pausing of a bacterial ribosome, the mRNA being translated is cleaved at a site within or immediately adjacent to the A site codon. The extent of this A site mRNA cleavage is correlated with the extent of ribosome pausing as assayed by tmRNA-mediated tagging of the nascent polypeptide. Cleavage does not require tmRNA, the ribosomal alarmone (p)ppGpp, or bacterial toxins such as RelE which have been shown to stimulate a similar activity. Translation is required for cleavage, suggesting that the ribosome participates in the reaction in some fashion. When normal protein synthesis is compromised, A site mRNA cleavage and the tmRNA system provide a mechanism for reducing translational errors and the production of aberrant and potentially harmful polypeptides.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Christopher S
CS
Hayes
Robert T
RT
Sauer
D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D003062:Codon / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics*; D038205:beta-Crystallin A Chain
D001427:Bacterial Toxins; D003062:Codon; D018388:Codon, Terminator; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; C465566:RelE protein, E coli; D038205:beta-Crystallin A Chain; C027627:guanosine-3',5'-bis(diphosphate) 3'-pyrophosphatase; D011755:Pyrophosphatases