Recruitment of a species-specific translational arrest module to monitor different cellular processes

Abstract

Nascent chain-mediated translation arrest serves as a mechanism of gene regulation. A class of regulatory nascent polypeptides undergoes elongation arrest in manners controlled by the dynamic behavior of the growing chain; Escherichia coli SecM monitors the Sec protein export pathway and Bacillus subtilis MifM monitors the YidC membrane protein integration/folding pathway. We show that MifM and SecM interact with the ribosome in a speciesspecific manner to stall only the ribosome from the homologous species. Despite this specificity, MifM is not exclusively designed to monitor membrane protein integration because it can be converted into a secretion monitor by replacing the N-terminal transmembrane sequence with a secretion signal sequence. These results show that a regulatory nascent chain is composed of two modular elements, one devoted to elongation arrest and another devoted to subcellular targeting, and they imply that physical pulling force generated by the latter triggers release of the arrest executed by the former. The combinatorial nature may assure common occurrence of nascent chain-mediated regulation.stalling sequence | SpoIIIJ | SecA | exit tunnel

Picky nascent peptides do not talk to foreign ribosomes

“…Although SecM and MifM peptides elicit the same ribosomal response-programmed translation arrest-they do not share any obvious homology. By using a cell-free translation system driven by either E. coli or B. subtilis ribosomes, Chiba et al (1) were able to show that the B. subtilis MifM nascent peptide prompts stalling of the B. subtilis ribosome but not of the foreign E. coli ribosome. Conversely, the SecM nascent peptide, which efficiently arrests progression of the homologous E. coli ribosome, fails to do so when translated by heterologous ribosomes from B. subtilis (Fig.…”

“…Chiba et al (1) in this issue of PNAS reveal that, at least in some cases, these dialogues can be species-specific.…”

“…Translation arrest directed by SecM and MifM peptides is influenced by dissimilar factorsthe activity of the secretion apparatus in the former case and membrane insertion in the latter case. However, Chiba et al (1) were able to dissociate ribosome stalling from the peptide's sensory properties. By replacing the N terminus of MifM with a secreted signal sequence, Chiba et al (1) converted MifM into a secretion sensor, thereby showing that the arrest domain operates independently of the peptide's sensory domain.…”

Hydrophilic microenvironment required for the channel-independent insertase function of YidC protein

“…Although SpoIIIJ and YidC2 share growth-essential functions, as indicated from the synthetic lethal phenotype of their deletion (8,9), SpoIIIJ is constitutively expressed and YidC2 is induced upon dysfunction of SpoIIIJ (10,11) in a manner that is repressible autogenously (12). MifM is encoded from the upstream ORF of yidC2 and plays an essential role in this cross-feedback and autogenous regulation by undergoing regulated elongation arrest in its translation (12)(13)(14). The ribosome stalling at mifM leads to exposure of the ShineDalgarno sequence of yidC2 to enhance its translation.…”

Strolling Toward New Concepts

“…While the ribosome uses wellconserved mechanisms for decoding and peptide bond formation, it also must deal with divergent proteome members in the reviewing process involving the exit tunnel. Shinobu Chiba showed that the MifM arrest sequence acts in a species-specific manner against the B. subtilis ribosome (21,98). It would seem difficult at present to predict which sequences might interact with the exit tunnel/active site regions of the ribosome.…”