Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; CIBSS - Centre for Integrative Biological Signalling Studies, University Freiburg, 79104 Freiburg, Germany.
Cell Rep. 2023 Mar 28;42(3):112140. doi: 10.1016/j.celrep.2023.112140. Epub 2023 Feb 25.
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.
信号序列依赖性蛋白靶向对于真核和原核细胞的时空组织至关重要，这一过程由信号识别颗粒（SRP）等专用蛋白靶向因子来辅助完成。然而，靶向信号不仅包含在蛋白质中，也可能存在于 mRNA 内。通过体内和体外实验，我们表明 mRNA 靶向受核苷酸含量和 mRNA 内二级结构的控制。mRNA 与细菌膜的结合不依赖于可溶性靶向因子，但依赖于 SecYEG 易位子和 YidC。重要的是，从膜结合 mRNA 翻译的蛋白质的膜插入不依赖于 SRP 途径，而后者对于从细胞质 mRNA 翻译的蛋白质是严格必需的。总之，我们的数据表明，mRNA 靶向与经典的 SRP 依赖性蛋白靶向平行作用，并且当 SRP 途径受损时，作为膜蛋白插入的替代策略。
