Abstract
Transfer RNAs are ancient molecules present in all domains of life. In addition to translating the genetic code into protein and defining the second genetic code together with aminoacyl-tRNA synthetases, tRNAs act in many other cellular functions. Robust phenomenological observations on the role of tRNAs in translation, together with massive sequence and crystallographic data, have led to a deeper physicochemical understanding of tRNA architecture, dynamics and identity. In vitro studies complemented by cell biology data already indicate how tRNA behaves in cellular environments, in particular in higher Eukarya. From an opposite approach, reverse evolution considerations suggest how tRNAs emerged as simplified structures from the RNA world. This perspective discusses what basic questions remain unanswered, how these answers can be obtained and how a more rational understanding of the function and dysfunction of tRNA can have applications in medicine and biotechnology.
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Acknowledgements
This perspective is based on an invited talk given at the 22nd tRNA Workshop in Uppsala (November 1–6, 2007). It has benefited from the input of my Strasbourg colleagues and students and the exchange over years of ideas and knowledge with many contributors from the tRNA community. Because of space limitations, all contributors could not be explicitly mentioned and I apologize for this. Particular thanks are due to C. Florentz, W. Hosseini and L. Kirsebom for comments on the manuscript. A. Gaudry and C. Sauter are acknowledged for help in figure preparation. This work was supported by the Centre National de la Recherche Scientifique, Université Louis Pasteur, and ACI BCMS “Code génétique: mieux connaître ses déviations pour comprendre son évolution.”
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Giegé, R. Toward a more complete view of tRNA biology. Nat Struct Mol Biol 15, 1007–1014 (2008). https://doi.org/10.1038/nsmb.1498
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DOI: https://doi.org/10.1038/nsmb.1498
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