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

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 di...

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Autores principales: Kulkarni, Prajna R., Jia, Tao, Kuehne, Sarah A., Kerkering, Thomas M., Morris, Elizabeth R., Searle, Mark S., Heeb, Stephan, Rao, Jayasimha, Kulkarni, Rahul V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066749/
https://www.ncbi.nlm.nih.gov/pubmed/24782516
http://dx.doi.org/10.1093/nar/gku309
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author Kulkarni, Prajna R.
Jia, Tao
Kuehne, Sarah A.
Kerkering, Thomas M.
Morris, Elizabeth R.
Searle, Mark S.
Heeb, Stephan
Rao, Jayasimha
Kulkarni, Rahul V.
author_facet Kulkarni, Prajna R.
Jia, Tao
Kuehne, Sarah A.
Kerkering, Thomas M.
Morris, Elizabeth R.
Searle, Mark S.
Heeb, Stephan
Rao, Jayasimha
Kulkarni, Rahul V.
author_sort Kulkarni, Prajna R.
collection PubMed
description 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.
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spelling pubmed-40667492014-06-24 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 A. Kerkering, Thomas M. Morris, Elizabeth R. Searle, Mark S. Heeb, Stephan Rao, Jayasimha Kulkarni, Rahul V. Nucleic Acids Res Computational Biology 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. Oxford University Press 2014-07-01 2014-04-29 /pmc/articles/PMC4066749/ /pubmed/24782516 http://dx.doi.org/10.1093/nar/gku309 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Computational Biology
Kulkarni, Prajna R.
Jia, Tao
Kuehne, Sarah A.
Kerkering, Thomas M.
Morris, Elizabeth R.
Searle, Mark S.
Heeb, Stephan
Rao, Jayasimha
Kulkarni, Rahul V.
A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title_full A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title_fullStr A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title_full_unstemmed A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title_short A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa
title_sort sequence-based approach for prediction of csra/rsma targets in bacteria with experimental validation in pseudomonas aeruginosa
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066749/
https://www.ncbi.nlm.nih.gov/pubmed/24782516
http://dx.doi.org/10.1093/nar/gku309
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