Investigating the relationship between mRNA degradation rates and secondary structure in mycobacteria

Kelly, Jessica M.

Student Work

Investigating the relationship between mRNA degradation rates and secondary structure in mycobacteria

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Mycobacterium tuberculosis (MTB) infections cause tuberculosis, one of the top ten causes of death worldwide. To survive stress conditions within the host, MTB regulates its transcriptome, which includes regulating mRNA degradation rates. In E. coli, it has been shown that secondary structures in 5’ Untranslated Regions (5’ UTRs) decrease the efficiency of mRNA degradation by hindering RppH and RNase E activity. In mycobacteria, the mechanisms regulating mRNA degradation are poorly understood, despite the presence of an RNase E homolog. In MTB, the mRNA coding for the virulence factor EsxB exhibits increased half-life following a cleavage event, relative to its parent transcript. We hypothesized that the increased stability is caused by formation of two terminal hairpin loops in the esxB 5’ UTR post-cleavage. Surprisingly, deletion of the esxB 5’ UTR loop structures did not increase the transcript degradation rate. Secondary structures in 5’ UTRs were also predicted computationally transcriptome-wide, and base pairing probabilities were calculated to identify structured regions. Similarly, no significant relationship between base pairing in 5’ UTRs and mRNA half-life were revealed in MTB or Mycobacterium smegmatis. However, unpaired regions in the ribosome binding site and start codon had a significant positive correlation with mRNA stability and ribosome binding, suggesting that translation efficiency may play a substantial role in controlling mRNA stability.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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