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Open Access Atomic Mutagenesis of the Ribosome: Towards a Molecular Understanding of Translation

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The multifaceted repertoire of non-protein-coding RNAs (ncRNAs) in organisms of all three domains of life emphasizes their fundamental role in biology. Research in my lab focuses on revealing the regulatory and catalytic function of small and large ncRNAs in different model organisms. In particular we are interested in understanding ncRNA/protein complexes such as the vault complex or the ribosome. The ribosome, the central enzyme of protein biosynthesis, is a multifunctional ribonucleoprotein particle composed of two unequal subunits that translates the genome's message into all proteins needed for life. The crucial role the translation machinery plays in gene expression is also mirrored by the fact that the ribosome represents the main target for antibiotics. Decades of genetic, biochemical and recent crystallographic studies revealed the ribosome as an RNA-enzyme with roots in the 'RNA world'. Despite these experimental insights, the catalytic and regulatory mechanisms of the ribosomal RNA are still not fully understood at the molecular level. To unravel the detailed contributions of rRNA nucleotides for protein synthesis we have developed and applied an 'atomic mutagenesis' approach. This tool allows the role of specific 23S rRNA functional groups and even individual atoms to be studied during various stages of the ribosomal elongation cycle with thus far unequalled precision. This experimental approach bridges the disciplines of biochemistry and organic chemistry and has recently revealed specific functional 23S rRNA groups involved in peptide bond synthesis, peptidyl-tRNA hydrolysis, GTPase activation, and tRNA translocation.
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Keywords: NUCLEOTIDE ANALOG INTERFERENCE; PROTEIN SYNTHESIS; RIBOSOME; RNA STRUCTURE AND FUNCTION

Document Type: Research Article

Affiliations: University of Bern Department of Chemistry and Biochemistry Freiestrasse 3 CH-3012 Bern, Switzerland. [email protected]

Publication date: May 1, 2013

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  • International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions

    CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.

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