- Restrictions on Access:
- Open Access.
- CsrA is an mRNA binding protein and key regulator of the carbon storage regulatory (Csr) system in Escherichia coli. The Csr system in E. coli is responsible for controlling the expression of various genes involved in carbon metabolism, motility, and biofilm formation. CsrA is known to be a repressor of gene expression. It represses gene expression by binding to its mRNA target, thereby preventing the ribosome from binding. This ultimately prevents translation from occurring. There has yet to be a reported case of CsrA-mediated translational activation until now. Transcriptomic studies revealed that ymdA has the strongest activation by CsrA across the E. coli transcriptome. CLIP-seq data also indicated that CsrA binds to ymdA in the 5 untranslated region (5 UTR) of its mRNA transcript. Further investigation showed that CsrA activates ymdA post-transcriptionally. Additionally, two critical CsrA binding sites were identified in the mRNA leader region of ymdA. Loss of binding at either of these two sites completely prevents CsrA-mediated activation of ymdA from occurring. Computational RNA structure prediction software identified a putative RNA hairpin that forms upstream of the ymdA start codon and sequesters the Shine-Dalgarno (SD) sequence, which would inhibit ribosome binding. Additionally, one of the two critical CsrA binding sites that were identified was predicted to be sequestered in this hairpin. Thus, when CsrA binds to this site, it destabilizes the hairpin thus freeing up the SD sequence for the ribosome to bind and therefore allowing translation to occur. This proposed model is consistent with our findings.
- Dissertation Note:
- B.S. Pennsylvania State University 2020.
- Technical Details:
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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