The mechanism by which the RNA degrading enzyme RNase E binds to the cell membrane is poorly understood. Work by Dr. Sue Lin-Chao and colleagues at the Institute of Molecular Biology, Academia Sinica, recently published in the Proceedings of the National Academy of Sciences of the United States of America elucidates this mechanism and links it to the degradation of RNA in bacteria.

　　Bacteria and eukaryotes share conserved RNA species (rRNA, tRNA and mRNA) and interacting partners that contribute to protein synthesis. However, bacterial RNA species are comparatively distributed throughout the cell. Despite the absence of membrane-bound organelles, key components of bacterial RNA processing and decay facilities are localized to specific subcellular compartments to ensure proper processing and decay. Much of the RNA processing and degradation activity in bacteria takes place in a single complex called the degradosome. Previously Dr. Lin-Chao’s group showed that the E. coli degradosome contains RNase E, the RhlB RNA helicase, polynucleotide phosphorylase (PNPase), and enolase (Miczak et al., 1996) and that the degradosome is tethered to the cytoplasmic membrane by the N-terminal region of RNase E (Liou et al., 2001). However, the function and nature of membrane binding and whether homologs from phylogenetically distant species of bacteria are also able to bind the membrane have not been investigated. In the recently published study, Dr. Lin-Chao and colleagues showed that a reconstituted, highly conserved N-terminal fragment (NRne, residues 1-499) of RNase E specifically bound to anionic phospholipids through electrostatic interactions. E. coli RNase G and RNase E/G homologs from phylogenetically distant bacteria like Aquifex aeolicus, Haemophilus influenzae Rd and Synechocystis sp. were also found to share these membrane-binding properties. Further, the NRne and its homologs have conserved electrostatic potentials that are highly positive and spread over a large surface area that encompasses four putative membrane-binding regions identified in the “large” domain consisting of the RNase H, S1, 5'-sensor, and DNase I subdomains of E. coli NRne. Interestingly, in vitro experiments revealed membrane-bound NRne possesses enhanced substrate affinity and a secondary structure that resists obvious thermotropic changes between 10 and 60°C while retaining normal cleavage activity after cooling. Dr. Lin-Chao’s group therefore concluded that NRne membrane binding induces protein secondary structure changes and enzymatic activation by stabilizing the protein folding state and increasing its binding affinity for its substrate. These studies clarify the role of membrane-binding in RNase E-mediated RNA processing and decay in bacteria.

　　The other authors include Drs. Oleg N. Murashko and Vladimir R. Kaberdin. These studies were funded by Academia Sinica and the National Science Council.

　　The original paper: Proc. Natl. Acad. Sci. U. S. A. 2012 109 (18):7019-7024.