“Why is tRNA U34 modifications so central to decoding?”
“Why is tRNA U34 modifications so central to decoding?”Eric Westhof
Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de biologie moléculaire et cellulaire du CNRS
5th July, 11:00 AM
MCB Seminar Room 3/14
Title: “Why is tRNA U34 modifications so central to decoding?”
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. On the basis of the biochemical and genetic data in the literature coupled with many crystal structures of fully active ribosomes, several nucleotide modifications, especially those at positions 34 and 37 of the anticodon loop, are now better understood molecularly. Depending on the codon box, the modifications at 37 stabilize AU-rich codon-anticodon pairs and maintain the coding frame. The modifications at 34 help to avoid miscoding and allow to decode purine-ending codons in split codon boxes by promoting base pairing that are accommodated within the structural constraints of the ribosomal grip at the decoding site. 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.