TY - JOUR
T1 - Transcript degradation and noise of small RNA-controlled genes in a switch activated network in Escherichia coli.
AU - Arbel-Goren, Rinat
AU - Tal, Asaf
AU - Parasar, Bibudha
AU - Dym, Alvah
AU - Costantino, Nina
AU - Munoz-Garcia, Javier
AU - Court, Donald L
AU - Stavans, Joel
N1 - We thank O. Biham and E. Levine for useful conversations, S. Gottesman, E. Masse, J. Cronan, T. Ha and H. Aiba for strains and P. Choppakatla for carrying out some of the experiments. Author contributions: R.A.G., A.D. and B.P. performed the experiments. R.A.G. analyzed the data. A.T. contributed analysis algorithm tools. D.L.C. and N.C. contributed the recombineered strains. J.M.G. analyzed data numerically. R.A.G., A.T. and D.L.C. contributed to the experimental design and interpretation. J.S. conceived the project and wrote the manuscript. All authors provided feedback on the manuscript. Israel Science Foundation [514415 to J.S.]; Feinberg Foundation Visiting Faculty Program ( to J.M.-G.); MICINN (Spain) [FIS2012-32349 to J.M.-G.]; Intramural Research Program of the National Institutes of Health (to D.L.C.); National Cancer Institute (to D.L.C.); Center for Cancer Research (to D.L.C.); Siegfried and Irma Ullman Professorial Chair ( to J. S.). Funding for open access charge: Israel Science Foundation.
PY - 2016/4/16
Y1 - 2016/4/16
N2 - Post-transcriptional regulatory processes may change transcript levels and affect cell-to-cell variability or noise. We study small-RNA downregulation to elucidate its effects on noise in the iron homeostasis network of Escherichia coli In this network, the small-RNA RyhB undergoes stoichiometric degradation with the transcripts of target genes in response to iron stress. Using single-molecule fluorescence in situ hybridization, we measured transcript numbers of the RyhB-regulated genes sodB and fumA in individual cells as a function of iron deprivation. We observed a monotonic increase of noise with iron stress but no evidence of theoretically predicted, enhanced stoichiometric fluctuations in transcript numbers, nor of bistable behavior in transcript distributions. Direct detection of RyhB in individual cells shows that its noise is much smaller than that of these two targets, when RyhB production is significant. A generalized two-state model of bursty transcription that neglects RyhB fluctuations describes quantitatively the dependence of noise and transcript distributions on iron deprivation, enabling extraction of in vivo RyhB-mediated transcript degradation rates. The transcripts' threshold-linear behavior indicates that the effective in vivo interaction strength between RyhB and its two target transcripts is comparable. Strikingly, the bacterial cell response exhibits Fur-dependent, switch-like activation instead of a graded response to iron deprivation.
AB - Post-transcriptional regulatory processes may change transcript levels and affect cell-to-cell variability or noise. We study small-RNA downregulation to elucidate its effects on noise in the iron homeostasis network of Escherichia coli In this network, the small-RNA RyhB undergoes stoichiometric degradation with the transcripts of target genes in response to iron stress. Using single-molecule fluorescence in situ hybridization, we measured transcript numbers of the RyhB-regulated genes sodB and fumA in individual cells as a function of iron deprivation. We observed a monotonic increase of noise with iron stress but no evidence of theoretically predicted, enhanced stoichiometric fluctuations in transcript numbers, nor of bistable behavior in transcript distributions. Direct detection of RyhB in individual cells shows that its noise is much smaller than that of these two targets, when RyhB production is significant. A generalized two-state model of bursty transcription that neglects RyhB fluctuations describes quantitatively the dependence of noise and transcript distributions on iron deprivation, enabling extraction of in vivo RyhB-mediated transcript degradation rates. The transcripts' threshold-linear behavior indicates that the effective in vivo interaction strength between RyhB and its two target transcripts is comparable. Strikingly, the bacterial cell response exhibits Fur-dependent, switch-like activation instead of a graded response to iron deprivation.
U2 - https://doi.org/10.1093/nar/gkw273
DO - https://doi.org/10.1093/nar/gkw273
M3 - مقالة
SN - 1362-4962
VL - 44
SP - 6707
EP - 6720
JO - Nucleic acids research
JF - Nucleic acids research
IS - 14
ER -