The effect of queuosine on tRNA structure and function

Computational modeling was performed to determine the potential function of the queuosine modification of tRNA found in wobble position 34 of tRNA(asp ), tRNA(asn), tRNA(his), and tRNA(tyr). Using the crystal structure of tRNA (asp) and a tRNA-tRNA-mRNA complex model, we show that the queuosine modifi cation serves as a structurally restrictive base for tRNA anticodon loop fl exibility. An extended intraresidue and intramolecular hydrogen bonding net work is established by queuosine. The quaternary amine of the 7-aminomethyl side chain hydrogen bonds with the base's carbonyl oxygen. This positions the dihydroxycyclopentenediol ring of queuosine in proper orientation for h ydrogen bonding with the backbone of the neighboring uridine 33 residue. Th e interresidue association stabilizes the formation of a cross-loop hydroge n bond between the uridine 33 base and the phosphoribosyl backbone of the c ytosine at position 36. Additional interactions between RNAs in the transla tion complex were studied with regard to potential codon context and codon bias effects. Neither steric nor electrostatic interaction occurs between a minoacyl- and peptidyl-site tRNA anticodon loops that are modified with que uosine. However, there is a difference in the strength of anticodon/codon a ssociations (codon bias) based on the presence or lack of queuosine in the wobble position of the tRNA. Unmodified (guanosine-containing) tRNA(asp) fo rms a very stable association with cytosine (GAC), but is much less stable in complex with a uridine-containing codon (GAU). Queuosine-modified tRNA(a sp) exhibits no bias for either of cognate codons GAC or GAU and demonstrat es a lower binding energy similar to the wobble pairing of guanosine-contai ning tRNA with a GAU codon. This is proposed to be due to the inflexibility of the queuosine-modified anticodon loop to accommodate proper positioning for optimal Watson-Crick type associations. A preliminary survey of codon usage patterns in oncodevelopmental versus housekeeping gene transcripts su ggests a significant difference in bias for the queuosine-associated codons . Therefore, the queuosine modification may have the potential to influence cellular growth and differentiation by codon bias-based regulation of prot ein synthesis for discrete mRNA transcripts.