Monitoring substrate enables real-time regulation of a protein localization pathway

FEMS Microbiol Lett. 2018 Jun 1;365(11). doi: 10.1093/femsle/fny109.

Abstract

Protein localization machinery supports cell survival and physiology, suggesting the potential importance of its expression regulation. Here, we summarize a remarkable scheme of regulation, which allows real-time feedback regulation of the machinery expression. A class of regulatory nascent polypeptides, called monitoring substrates, undergoes force-sensitive translation arrest. The resulting ribosome stalling on the mRNA then affects mRNA folding to expose the ribosome-binding site of the downstream target gene and upregulate its translation. The target gene encodes a component of the localization machinery, whose physical action against the monitoring substrate leads to arrest cancellation. Thus, this scheme of feedback loop allows the cell to adjust the amount of the machinery to correlate inversely with the effectiveness of the process at a given moment. The system appears to have emerged late in evolution, in which a narrow range of organisms selected a distinct monitoring substrate-machinery combination. Currently, regulatory systems of SecM-SecA, VemP-SecDF2 and MifM-YidC2 are known to occur in different bacterial species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria / genetics*
  • Bacteria / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Secretion Systems / genetics*
  • Bacterial Secretion Systems / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Gene Expression Regulation, Enzymologic
  • Protein Biosynthesis
  • Protein Transport*
  • Transcription, Genetic

Substances

  • Bacterial Proteins
  • Bacterial Secretion Systems