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Review
, 11 (2), 134-40

tRNA's Modifications Bring Order to Gene Expression

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Review

tRNA's Modifications Bring Order to Gene Expression

Estella M Gustilo et al. Curr Opin Microbiol.

Abstract

The posttranscriptional modification of RNA is a significant investment in genes, enzymes, substrates, and energy. Advances in molecular genetics and structural biology indicate strongly that modifications of tRNA's anticodon domain control gene expression. Modifications at the anticodon's wobble position are required for recognition of rarely used codons and restrict or expand codon recognition depending on their chemistries. A shift of the translational reading frame occurs in the absence of modifications at either wobble position-34 or the conserved purine-37, 3'-adjacent to the anticodon, causing expression of alternate protein sequences. These modifications have in common their contribution of order to tRNA's anticodon.

Figures

Figure 1
Figure 1
Modifications of the anticodon stem and loop (ASL) of tRNA order the loop preventing frameshifting and allowing for accurate codon selection. (a) Modifications such as s2C at (◙), s2U34, mnm5U34, cmo5U34 and Q at wobble position-34 (◙) and t6A, m1G, ms2io6A and yW at position-37 (◙) structure the anticodon toward the canonical “U-turn (at invariant U33) and increase stability by facilitating the stacking of the aromatic nucleoside bases of positions 34–37. Purine-37 modifications negate intra-loop base pairing (…). (b) Representative prokaryotic modified nucleosides that are involved in control of rare codon recognition and reading frame maintenance/frameshifting. The chemical structures and locations (positions 32, 34 or 37) of the modifications in tRNA’s anticodon domain are shown. Abbreviated names are defined in the text. Eukaryotic modifications with similar chemistries, such as mcm5s2U, can be found at the RNA Modification Database (URL: http://library.med.utah.edu/RNAmods/).
Figure 2
Figure 2
The Universal Genetic Code. Figure. The 61 sense codons are color shaded according to extent of degeneracy: single codes are in grey (□); twofold degenerate codes, pink (□); threefold, yellow (□); fourfold, green (□); two- plus fourfold or 6-fold degenerate codes in blue (□). The stop codons are in red. Accurate and efficient recognition of codons are dependent on the specific modifications at the anticodon stem and loop (ASL) of tRNA and the modifications’ ability to restrict or expand codon box recognition. Rare codons that are discussed are in bold.
Figure 3
Figure 3
The dual error model of frameshifting (adapted from [44]). (a) In place of a hypomodified cognate tRNA, an unmodified near-cognate tRNA binds to the A-site of the ribosome causing a pause after translocation to the P-site. Following this, a −1 or +1 frameshift is triggered. (b) The hypomodified tRNA evolves at a slow pace and failed to bind to the A-site. As a result the cognate tRNA is paused and a −1/+1 frameshifting is induced. (c) As opposed to the first case (a), the hypomodified tRNA successfully binds to the A site and after translocation to the P-site a frameshift is produced.

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