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Exploring the functional relationship between MazF and tmRNA

by
Sarak Baik
B.Sc. Political Science, 1994
University of Houston



Thesis Advisor: Masayori Inouye, Ph.D.
Graduate Program in Biochemistry and Molecular Biology

CABM Room 341
Piscataway

Thursday, July 22, 2010
10:00 am


Abstract

The toxin MazF in Escherichia coli cleaves single-strand RNAs specifically at ACA sequences. MazF overexpression virtually eliminates all cellular mRNAs to completely block protein synthesis. However, protein synthesis can continue on an mRNA that is devoid of ACA triplets. That ribosomal RNAs remain intact, in the face of complete translation arrest, suggested a purpose for such preservation. We therefore examined the sequence of all transcribed RNAs to determine if there were any statistically significant bias against ACA. While ACA motifs are absent from transfer-messenger RNA (tmRNA), 4.5S RNA, and seven of the eight 5S rRNA, statistical analysis revealed that only in tmRNA was the absence non-random. Introduction of single-strand ACAs make tmRNA highly susceptible to MazF cleavage. Furthermore, analysis of tmRNA sequences from 442 bacteria showed that the discrimination against ACA in tmRNAs was seen mostly in enterobacteria. We propose that the unusual bias against ACA in tmRNA may have co-evolved with the acquisition of MazF.


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