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Distal effects in RNase P RNA mediated cleavage
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-95833OAI: oai:DiVA.org:uu-95833DiVA: diva2:170186
Available from: 2007-04-27 Created: 2007-04-27 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Versatile and Antique World of RNA: The Simplicity of RNA Mediated Catalysis
Open this publication in new window or tab >>Versatile and Antique World of RNA: The Simplicity of RNA Mediated Catalysis
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

RNA is the only biological molecule that can function both as a repository of information and as a catalyst. This, together with the ability to self-replicate, led to recognition of RNA as ‘prelude to life’.

My work highlights some of the important features of RNA as a catalyst, exemplified by RNase P. It addresses questions of evolutionary preservations of residues and structure, involvement of metal ions and finally structure evolution towards minimal catalytically competent RNA motifs.

RNase P is the only enzyme involved in 5’ end processing of all pre-tRNAs. Until recently, it was believed that the RNA moiety of RNase P is responsible for mediating catalysis only in Bacteria. However, my recent study conclusively demonstrated that eukaryotic RNase P RNA is catalytically competent in vitro in absence of proteins. These findings evidenced evolutionary preservation of RNA-mediated catalysis in RNase P.

RNase P RNA is a metalloeznyme. In my studies I analyzed the contributions of individual chemical groups at the cleavage site to catalysis. My findings suggested that the 2’OH of N-1 and the exocyclic amine of G+1 are involved in positioning of functionally important metal ions. Additionally, data appointed the function of Pb2+ as both structural metal ion and important in generating the nucleophile. My studies further indicate a conformational change upon RNase P RNA -substrate complex formation in keeping with an induced fit mechanism.

Studying the effects of reducing the ribozyme size upon dissection of bacterial RNase P RNAs, we defined the smallest catalytically competent domain i.e. P15-loop. Derivatives of this autonomous metal ion binding domain, (the smallest being 31nt-s), are able to cleave both whole-length pre-tRNAs as well as hairpin substrates, though with severely reduced rates relative to their parent ribozymes. The study has inferred that partite ES interactions at the cleavage site prove sufficient for catalysis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 82 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 298
Microbiology, RNA Catalysis, RNase P, Metal ions, tRNA Processing, Ribozyme, Mikrobiologi
urn:nbn:se:uu:diva-7847 (URN)978-91-554-6879-8 (ISBN)
Public defence
2007-05-22, C10:301, Biomedical Centre, Husargatan 3, Uppsala, 10:00
Available from: 2007-04-27 Created: 2007-04-27Bibliographically approved

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