mRNA targeting eliminates the need for the signal recognition particle during membrane protein insertion in bacteria

• Published in: Cell reports (Cambridge) 2023-03, Vol.42 (3), p.112140-112140, Article 112140
• Main Authors: Sarmah, Pinku, Shang, Wenkang, Origi, Andrea, Licheva, Mariya, Kraft, Claudine, Ulbrich, Maximilian, Lichtenberg, Elisabeth, Wilde, Annegret, Koch, Hans-Georg
• Format: Article
• Language: English
• Subjects: (p)ppGpp; alarmones; Bacteria - metabolism; Bacterial Proteins - metabolism; CP: Microbiology; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; FtsY; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Transport Proteins - metabolism; mRNA targeting; Protein Transport; Ribosomes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; SEC Translocation Channels - genetics; SEC Translocation Channels - metabolism; SecYEG translocon; signal recognition particle; Signal Recognition Particle - genetics; Signal Recognition Particle - metabolism; small membrane proteins; stringent response; translation; YidC
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112140

Signal-sequence-dependent protein targeting is essential for the spatiotemporal organization of eukaryotic and prokaryotic cells and is facilitated by dedicated protein targeting factors such as the signal recognition particle (SRP). However, targeting signals are not exclusively contained within proteins but can also be present within mRNAs. By in vivo and in vitro assays, we show that mRNA targeting is controlled by the nucleotide content and by secondary structures within mRNAs. mRNA binding to bacterial membranes occurs independently of soluble targeting factors but is dependent on the SecYEG translocon and YidC. Importantly, membrane insertion of proteins translated from membrane-bound mRNAs occurs independently of the SRP pathway, while the latter is strictly required for proteins translated from cytosolic mRNAs. In summary, our data indicate that mRNA targeting acts in parallel to the canonical SRP-dependent protein targeting and serves as an alternative strategy for safeguarding membrane protein insertion when the SRP pathway is compromised. [Display omitted] •Nucleotide composition and secondary structures determine mRNA targeting•The SecYEG translocon and the YidC insertase act as mRNA receptors in bacteria•mRNA targeting enables SRP-independent membrane protein insertion Protein targeting is generally believed to depend on targeting information that is retained within the protein itself. Sarmah et al. now show that mRNA targeting contributes to membrane protein insertion in bacteria and that it provides an alternative strategy when the canonical signal recognition particle-dependent protein-targeting pathway is saturated or inhibited.