The Cold shock protein A, CspA, is a major cold shock protein and was shown to be detected only during early-log-phase growth at 37°C and during log phase after a shift from 37°C to 10°C [5, 6]. However, studies have shown that although the expression of cspA is reduced during stationary phase, cspA mRNA and CspA are detectable during all growth phases . CspA acts as a positive transcription factor of at least two cold shock genes: hns [2, 3, 4] and gyrA . cspA has been shown to negatively regulate its own expression as the result of attenuation of transcription . A model of how CspA might affect the transcription of hns has been proposed .
CspE inhibits the expression of cspA in vitro by increasing pause recognition for RNA polymerase at the cspA cold box . cspA expression was increased in a uvrY mutant strain and reduced when uvrY was overexpressed .Read more >
CspA belongs to the cold shock family of proteins and was shown to be homologous to eukaryotic Y-box transcription factors [12, 13]. The transcription factors of this family recognize a CCAAT sequence in the regulatory region of the genes regulated [2, 3].
The crystal structure of CspA has been determined by X-ray crystallography to a resolution of 2.0 Å ; also, the structure of CspA has been determined by NMR spectroscopy [15, 16].
On other hand, Jiang et al. in 1997 demonstrated that CspA acts as an RNA chaperone that prevents secondary structure formation of RNA at low temperatures [8, 17]. cspA is not only expressed at low temperatures but also at 37°C during nutritional up-shift conditions, until the cells start dividing . cspA mRNA is very unstable at 37°C and rapidly disappears as the cell density and RNase activity increase [19, 20]. The lability of cspA mRNA at high temperatures is mediated by cleavage toward its 3' end; this cleavage is partially dependent on RNase E . Thus, cspA expression levels change in response to temperature fluctuations . The long 5' untranslated region of cspA mRNA contains a feature within the first 25 bases that is responsible for derepression of cspA expression and inhibition of synthesis of cellular proteins other than cold shock proteins following cold shock . cspA was also shown to be induced by addition of chloramphenicol and was induced even in the absence of protein synthesis [24, 25].
By making use of microarrays analysis, Constantinidou et al.  concluded that FNR represses cspA gene expression, but it is not known which of the two promoters (cspAp1, cspAp2) is affected. The authors also identified a putative FNR-binding site upstream of the gene, but the sequence was not reported.
Fis and HNS activate and repress cspA transcription, respectively, and their effects cancel each other when they act together, resulting in basal activity of cspA .
|Connectivity class:||Local Regulator|
|Length:||213 bp / 70 aa|
|TU(s) encoding the TF:||
|Regulated gene(s)||gyrA, hns|
|Multifun term(s) of regulated gene(s)||
MultiFun Term (List of genes associated to the multifun term)
Transcription related (2)
DNA replication (1)
nucleoproteins, basic proteins (1)
|Regulated operon(s)||gyrA, hns|
|First gene in the operon(s)||gyrA, hns|
|Simple and complex regulons|
|Simple and complex regulatory phrases||
Regulatory phrase (List of promoters regulated by the phrase)
|Functional conformation||Function||Promoter||Sigma factor||Central Rel-Pos||Distance to first Gene||Genes||Sequence
||LeftPos||RightPos||Evidence (Confirmed, Strong, Weak)||References|
|CspA||activator||hnsp||Sigma70||nd||nd||hns||nd||nd||[BPP]||, , |
|Evolutionary conservation of regulatory elements|
 La Teana A., Brandi A., Falconi M., Spurio R., Pon CL., Gualerzi CO., 1991, Identification of a cold shock transcriptional enhancer of the Escherichia coli gene encoding nucleoid protein H-NS., Proc Natl Acad Sci U S A. 88(23):10907-11
 Bae W., Phadtare S., Severinov K., Inouye M., 1999, Characterization of Escherichia coli cspE, whose product negatively regulates transcription of cspA, the gene for the major cold shock protein., Mol Microbiol. 31(5):1429-41
 Zere TR., Vakulskas CA., Leng Y., Pannuri A., Potts AH., Dias R., Tang D., Kolaczkowski B., Georgellis D., Ahmer BM., Romeo T., 2015, Genomic Targets and Features of BarA-UvrY (-SirA) Signal Transduction Systems., PLoS One. 10(12):e0145035
 Didier DK., Schiffenbauer J., Woulfe SL., Zacheis M., Schwartz BD., 1988, Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box., Proc Natl Acad Sci U S A. 85(19):7322-6
 Newkirk K., Feng W., Jiang W., Tejero R., Emerson SD., Inouye M., Montelione GT., 1994, Solution NMR structure of the major cold shock protein (CspA) from Escherichia coli: identification of a binding epitope for DNA., Proc Natl Acad Sci U S A. 91(11):5114-8
 Feng W., Tejero R., Zimmerman DE., Inouye M., Montelione GT., 1998, Solution NMR structure and backbone dynamics of the major cold-shock protein (CspA) from Escherichia coli: evidence for conformational dynamics in the single-stranded RNA-binding site., Biochemistry. 37(31):10881-96
 Brandi A., Giangrossi M., Giuliodori AM., Falconi M., 2016, An Interplay among FIS, H-NS, and Guanosine Tetraphosphate Modulates Transcription of the Escherichia coli cspA Gene under Physiological Growth Conditions., Front Mol Biosci. 3:19
 Hankins JS., Zappavigna C., Prud'homme-Genereux A., Mackie GA., 2007, Role of RNA structure and susceptibility to RNase E in regulation of a cold shock mRNA, cspA mRNA., J Bacteriol. 189(12):4353-8
 Jiang W., Fang L., Inouye M., 1996, The role of the 5'-end untranslated region of the mRNA for CspA, the major cold-shock protein of Escherichia coli, in cold-shock adaptation., J Bacteriol. 178(16):4919-25
 Etchegaray JP., Inouye M., 1999, CspA, CspB, and CspG, major cold shock proteins of Escherichia coli, are induced at low temperature under conditions that completely block protein synthesis., J Bacteriol. 181(6):1827-30
 Constantinidou C., Hobman JL., Griffiths L., Patel MD., Penn CW., Cole JA., Overton TW., 2006, A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth., J Biol Chem. 281(8):4802-15