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Regulation and physiological role of SsrA RNA

by Hong, Sue-Jean.

Abstract (Summary)
The last decade has witnessed a renaissance in the field of small regulatory RNAs. All organisms ranging from bacteria to human contain a wealth of small regulatory RNAs that function in a variety of cellular processes. The small regulatory RNAs are involved in regulation of gene expression at both transcriptional and post-transcriptional levels, by modifying chromatin structure, modulating transcription factor activity, and influencing mRNA stability, processing, and translation. One of the most interesting of these small regulatory RNAs is SsrA RNA. SsrA with properties of both a tRNA and an mRNA carries out an extraordinary transtranslation reaction that is ubiquitous in bacteria. In cases where a ribosome is arrested on a selected mRNA, SsrA is recruited to the A site of the ribosome. By an unknown mechanism, SsrA causes the ribosome to release the mRNA and resume translation using a short open reading frame encoded within SsrA. This process serves to release the stalled ribosome and adds a peptide tag to the end of the nascent polypeptide marking it for degradation. This unique activity is required for such cellular processes as growth and development, pathogenesis, symbiosis, and stress tolerance. This study focuses on the regulation and physiological function of SsrA using Caulobacter crescentus as a model organism. Asymmetric cell division and differentiation of C. crescentus and the extensive knowledge of the molecular events associated with the cell cycle provide an unique opportunity to study the influence of SsrA activity on cell physiology. In C. crescentus, the initiation of chromosomal replication is delayed during G1-S transition in the absence of SsrA activity. SsrA is also iii required for plasmid replication. The steady-state levels of SsrA is cell cycle regulated such that its expression is high in both G1 and G2 phases but low in S phase. Through detailed analysis of effects of two highly conserved proteins, RNase R and SmpB, on the regulation of the abundance of SsrA, it has been demonstrated that SsrA is specifically degraded by RNase R at a specific point in the cell cycle and this timing may be regulated by SmpB. Proteomic studies of cellular substrates of SsrA reveal that proteins in diverse functional categories are tagged by SsrA and at least one consensus DNA motif exists that may activate the SsrA system. Genetic and proteomic analyses suggest that SsrA may control plasmid replication by regulating the replication initiation protein, Rep. Taken together, this study establishes a foundation for a more comprehensive understanding of the regulation and physiological role of the small regulatory RNA, SsrA. iv
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School:Pennsylvania State University

School Location:USA - Pennsylvania

Source Type:Master's Thesis

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