Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri

The role of small RNAs as critical components of global regulatory networks has been highlighted by several recent studies. An important class of such small RNAs is represented by CsrB and CsrC of Escherichia coli, which control the activity of the global regulator CsrA. Given the critical role played by CsrA in several bacterial species, an important problem is the identification of CsrA-regulating small RNAs. In this paper, we develop a computer program (CSRNA-FIND) designed to locate potential CsrA-regulating small RNAs in bacteria. Using CSRNA-FIND to search the genomes of bacteria having homologs of CsrA, we identify all the experimentally known CsrA-regulating small RNAs and also make predictions for several novel small RNAs. We have verified experimentally our predictions for two CsrA-regulating small RNAs in Vibrio fischeri. As more genomes are sequenced, CSRNA-FIND can be used to locate the corresponding small RNAs that regulate CsrA homologs. This work thus opens up several avenues of research in understanding the mode of CsrA regulation through small RNAs in bacteria.