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A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa

Kulkarni, Prajna R.; Jia, Tao; Kuehne, Sarah H.; Kerkering, Thomas M.; Morris, Elizabeth R.; Searle, Mark S.; Heeb, Stephan; Rao, Jayasimha; Kulkarni, Rahul V.

Authors

Prajna R. Kulkarni

Tao Jia

Sarah H. Kuehne

Thomas M. Kerkering

Elizabeth R. Morris

Mark S. Searle

Jayasimha Rao

Rahul V. Kulkarni



Abstract

CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the production and secretion of virulence factors in diverse bacterial species. While direct messenger RNA binding by CsrA/RsmA has been studied in detail for some genes, it is anticipated that there are numerous additional, as yet undiscovered, direct targets that mediate its global regulation. To assist in the discovery of these targets, we propose a sequence-based approach to predict genes directly regulated by these regulators. In this work, we develop a computer code (CSRA TARGET) implementing this approach, which leads to predictions for several novel targets in Escherichia coli and Pseudomonas aeruginosa. The predicted targets in other bacteria, specifically Salmonella enterica serovar Typhimurium, Pectobacterium carotovorum and Legionella pneumophila, also include global regulators that control virulence in these pathogens, unraveling intricate indirect regulatory roles for CsrA/RsmA.We have experimentally validated four predicted RsmA targets in P. aeruginosa. The sequence-based approach developed in this work can thus lead to several testable predictions for direct targets of CsrA homologs, thereby complementing and accelerating efforts to unravel global regulation by this important family of proteins.

Journal Article Type Article
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 42
Issue 11
APA6 Citation Kulkarni, P. R., Jia, T., Kuehne, S. H., Kerkering, T. M., Morris, E. R., Searle, M. S., …Kulkarni, R. V. (in press). A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa. Nucleic Acids Research, 42(11), https://doi.org/10.1093/nar/gku309
DOI https://doi.org/10.1093/nar/gku309
Publisher URL http://nar.oxfordjournals.org/content/42/11/6811
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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