tRNA Modifications and Decoding Errors

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• Professor Eric Westhof (Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg)
• Wednesday 20 February 2019, 16:00-18:00
• Jean Thomas Lecture Theatre, Sanger Biochemistry Building.

If you have a question about this talk, please contact Mairi Kilkenny.

Ribosomal translation occurs through complex molecular interaction networks between mRNA, tRNA, and rRNA. Among those, the stability of codon-anticodon triplets, the conformation of the anticodon stem-loop of tRNA, the modified nucleotides, and the interactions with bases of rRNA at the decoding site form key contributors. Because the cellular activities of several enzymatic complexes are required for the maintenance of active ribosomes as well as of the pool of matured and modified tRNAs, ribosomal translation is intimately integrated within the biochemical, metabolic and cellular evolution processes in extant organisms. On the basis of many crystal structures of fully active ribosomes, nucleotide modifications, especially at positions 34 and 37 of the anticodon loop, are now better understood molecularly. Depending on the codon box, the modifications stabilize AU-rich codon-anticodon pairs and maintain the coding frame. They also contribute to the decoding of purine-ending codons in split codon boxes and help to avoid miscoding. Overall, the tRNA modifications allow for diversity in codon usage depending on genomic GC content as well as on the number and types of isoacceptor tRNAs. Although universal, the genetic code is not translated identically and differences exist not only between organisms in the three kingdoms of life but also between cellular types. To decipher diversely but efficiently the genetic code, cells developed sophisticated arrays between tRNA pools and tRNA modifications, anchored in the cellular metabolic enzymatic pathways and guaranteeing protein homeostasis. Examples of mutations that lead to specific human diseases in some of those enzymes will be described.

This talk is part of the Experimental and Computational Aspects of Structural Biology and Applications to Drug Discovery series.

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