Browsing by Author "Mishra, Madhup"

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    The Role of Free Energy Synchronization Signal in Translation of Prokaryotes
    (2004-05-19) Mishra, Madhup; Donald L. Bitzer, Committee Chair; Mladen A. Vouk, Committee Co-Chair; Steffen Heber, Committee Member
    Sequences upstream of the coding region in prokaryotes show a consensus sequence called the Shine Dalgarno sequence. This sequence is the Watson-Crick complement to the 3' tail of 16S ribosomal RNA. Rosnick analyzed the ensemble free energy scores between the 3' tail-end of the RNA and the underlying mRNA. He found that the affinity between the tail-end and the mRNA is not just restricted to the upstream Shine Dalgarno region (SD region), but also extends downstream throughout the length of the gene. He confirmed the SD region as the lock signal and found an ensemble periodic free energy signal called the synchronization signal in the downstream region with a harmonic that peaks every third nucleotide with respect to the start codon. The periodic signal is hypothesized to either have a role in keeping the ribosome in frame with the mRNA being translated, or being a good predictive indicator of that state. The current work: •Studies the hypothesis that the lock and the periodic signal seen in the ensemble of the species coding regions extends beyond just E.coli. Specifically the work is concerned with analysis of sample of species across bacteria and archae kingdoms of the prokaryotes. The analysis shows that the periodic signal is present in the coding regions but not in the non-coding regions and that in some cases a lock signal is not present. This work proposes an Exponential Binding Index Locking Model to account for the genes with no upstream lock signal. •Proposes a novel methodology for analysis of the synchronization signal over individual genes. The approach leverages the ensemble periodicity information through sinusoidal wave interpolation with frequency of 1/3rd to approximate the synchronization signal and study its magnitude and phase characteristics. The synchronization signal is seen as a good indicator of the process of translation as suggested by our investigations. The starting phase of the signal is dependent on the frame in which the Shine Dalgarno lock, where present happens upstream of start. An application of individual synchronization signal is identification of frameshifts in general in genes.The +1 programmed frameshifting gene prfB of E.Coli K12 was used as a case study to demonstrate this application.