A ribosome-nascent chain sensor of membrane protein biogenesis in Bacillus subtilis

• Published in: The EMBO journal Vol. 28; no. 22; pp. 3461 - 3475
• Main Authors: Chiba, Shinobu, Lamsa, Anne, Pogliano, Kit
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 18.11.2009; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Bacillus subtilis; Bacillus subtilis - genetics; Bacillus subtilis - metabolism; Bacteria; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Biosynthesis; E coli; Escherichia coli; Gene Expression Regulation, Bacterial; Genetics; membrane protein insertion; Membrane Proteins - biosynthesis; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Membranes; Models, Biological; Molecular biology; Molecular Sequence Data; Nucleic Acid Conformation; Oxa1p/Alb3/YidC; Protein Biosynthesis - genetics; Protein Biosynthesis - physiology; Protein folding; ribosome; Ribosomes - metabolism; SecM; translational regulation; Up-Regulation
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2009.280

Proteins in the YidC/Oxa1/Alb3 family have essential functions in membrane protein insertion and folding. Bacillus subtilis encodes two YidC homologs, one that is constitutively expressed (spoIIIJ/yidC1) and a second (yqjG/yidC2) that is induced in spoIIIJ mutants. Regulated induction of yidC2 allows B. subtilis to maintain capacity of the membrane protein insertion pathway. We here show that a gene located upstream of yidC2 (mifM/yqzJ) serves as a sensor of SpoIIIJ activity that regulates yidC2 translation. Decreased SpoIIIJ levels or deletion of the MifM transmembrane domain arrests mifM translation and unfolds an mRNA hairpin that otherwise blocks initiation of yidC2 translation. This regulated translational arrest and yidC2 induction require a specific interaction between the MifM C‐terminus and the ribosomal polypeptide exit tunnel. MifM therefore acts as a ribosome–nascent chain complex rather than as a fully synthesized protein. B. subtilis MifM and the previously described secretion monitor SecM in Escherichia coli thereby provide examples of the parallel evolution of two regulatory nascent chains that monitor different protein export pathways by a shared molecular mechanism.