A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties

Abstract

Regulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical roles in pathogenic bacterial virulence and are potential antibacterial targets. RNase E consists of a highly conserved catalytic domain and a variable non-catalytic domain that functions as the structural scaffold for the multienzyme degradosome complex. Despite conservation of the catalytic domain, a recent study identified differences in the response of RNase E homologues from different species to the same inhibitory compound(s). While RNase E from Escherichia coli has been well-characterised, far less is known about RNase E homologues from other bacterial species. In this study, we structurally and biochemically characterise the RNase E catalytic domains from four pathogenic bacteria: Yersinia pestis , Francisella tularensis , Burkholderia pseudomallei and Acinetobacter baumannii , with a view to exploiting RNase E as an antibacterial target. Bioinformatics, small-angle x-ray scattering and biochemical RNA cleavage assays reveal globally similar structural and catalytic properties. Surprisingly, subtle species-specific differences in both structure and substrate specificity were also identified that may be important for the development of effective antibacterial drugs targeting RNase E.

Targeting of the Essential acpP, ftsZ, and rne Genes in Carbapenem-Resistant Acinetobacter baumannii by Antisense PNA Precision Antibacterials

“…RNase E is an essential bacterial endoribonuclease involved in the turnover of messenger RNA and the maturation of structured RNA precursors (rRNA and tRNA processing) in E. coli [ 23 , 24 ]. The major initiator of bacterial mRNA decay is considered to be a multi-protein complex termed the RNA degradosome.…”

“…RNase E, coded for by the rne gene, is a central enzyme in RNA processing and metabolism [ 23 , 29 ], and therefore constitute a possible and interesting, but unexplored target for future precision antisense antibiotics. The present results demonstrate that antimicrobial anti- rne BPP-PNAs with MIC values of 2 μM against CRA can be found and may indeed be worth pursuing further.…”

Proteomic Analyses of Acinetobacter baumannii Clinical Isolates to Identify Drug Resistant Mechanism

“…EF-Tu and ribosomal protein can help the production of bacterial protein, and some study have found them upregulated in carbapenem-resistant strains ( Tiwari et al., 2012 ). RNase can perform different processing on RNA to regulate gene expression ( Mardle et al., 2019 ). Valyl-tRNA synthetase is responsible for the aminoacylation of tRNA ( Heck and Hatfield, 1988 ).…”

Heterozygous mutation SLFN14 K208N in mice mediates species-specific differences in platelet and erythroid lineage commitment

“…Previous studies found that endoribonuclease function is critical in RNA regulation in various bacterial species; however, to our knowledge, this is the first discovery of endoribonuclease-mediated species differences in mammals. 28,29 SLFN14 K219N patients have a high IPF, suggesting that thrombopoiesis is not sufficient to maintain steady levels of platelet production or that platelet clearance is accelerated. Platelets contain residual RNA from their predecessors, MKs, which form beaded extensions into the lumen of bone marrow sinusoids (proplatelets) and subsequent shear forces of the bloodstream that cause release of preplatelets and platelets into the blood.…”