title: Central role for RNase YbeY in Hfq-dependent and Hfq-independent small-RNA regulation in bacteria.
abstract: BACKGROUND
  Conceptual parallels exist between bacterial and eukaryotic small-RNA (sRNA) pathways, yet relatively little is known about which protein may recognize and recruit bacterial sRNAs to interact with targets. In eukaryotes, Argonaute (AGO) proteins discharge such functions. The highly conserved bacterial YbeY RNase has structural similarities to the MID domain of AGOs. A limited study had indicated that in Sinorhizobium meliloti the YbeY ortholog regulates the accumulation of sRNAs as well as the target mRNAs, raising the possibility that YbeY may play a previously unrecognized role in bacterial sRNA regulation.
  
  
  RESULTS
  We have applied a multipronged approach of loss-of-function studies, genome-wide mRNA and sRNA expression profiling, pathway analysis, target prediction, literature mining and network analysis to unravel YbeY-dependent molecular responses of E. coli exposed to hydroxyurea (HU). Loss of ybeY function, which results in a marked resistance to HU, had global affects on sRNA-mediated gene expression. Of 54 detectable E. coli sRNAs in our microarray analysis, 30 sRNAs showed a differential expression upon HU stress, of which 28 sRNAs displayed a YbeY-dependent change in expression. These included 12 Hfq-dependent and 16 Hfq-independent sRNAs. We successfully identified at least 57 experimentally inferred sRNA-mRNA relationships. Further applying a 'context likelihood of relatedness' algorithm, we reverse engineered the YbeY-dependent Hfq-dependent sRNA-mRNA network as well as YbeY-dependent Hfq-independent sRNA-mRNA network.
  
  
  CONCLUSIONS
  YbeY extensively modulates Hfq-dependent and independent sRNA-mRNA interactions. YbeY-dependent sRNAs have central roles in modulating cellular response to HU stress.
authors: Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur Campus, Mohanpur, Nadia, West Bengal 741252, India. sppandey@iiserkol.ac.in.
authors: Shree P
authors: SP
authors: Pandey
authors: Jonathan A
authors: JA
authors: Winkler
authors: Hu
authors: H
authors: Li
authors: Diogo M
authors: DM
authors: Camacho
authors: James J
authors: JJ
authors: Collins
authors: Graham C
authors: GC
authors: Walker
mesh_terms: D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D035001:Host Factor 1 Protein / Q000235:genetics* / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology*; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism; D012329:RNA, Bacterial / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; D008667:Metalloproteins; D012329:RNA, Bacterial; C510617:YbeY protein, E coli; D006918:Hydroxyurea