Transfer RNA Structure

Abstract

Transfer ribonucleic acid (tRNA) molecules that participate in the elongation step of protein synthesis on the ribosome have a conserved secondary structure, known as the cloverleaf, and fold into a common three‐dimensional architecture. The conservation of the global L‐shaped 3D fold is assessed by the more than 100 available crystal structures showing tRNAs in native states or in complexes where tRNAs are bound to various interacting systems such as cognate synthetases, editing, modification and processing enzymes or full ribosomes. These tRNA crystal structures display a whole range of structural adaptability features encoded in their sequence and underlying their various functions. Thus, as the number of available structural data expands, the concept of a unique tRNA structure fades out for that of an ensemble of interconnected and environmentally dependant tRNA structures.

Key Concepts:

  • tRNAs display a huge sequence variability.

  • tRNA molecules fold with a conserved secondary structure.

  • The conservation of the secondary structure originatesbase covariations in Watson–Crick pairs of helices.

  • The tertiary folds of tRNAs present a striking adaptability.

  • The structural adaptabilities of tRNAs stem from the molecular neutrality present among the various noncovalent interactions.

  • Only a minimal number of conserved tertiary interactions are preserved.

  • The maintenance of some non‐Watson–Crick pairs is key for the three‐dimensional structure.

  • As a consequence of structural adaptability, tRNAs have acquired a greatdiversity in biological systems.

  • The structure and function of tRNAs is modulated by the type and concentration of the ions surrounding them.

Keywords: transfer ribonucleic acid; tRNA; cloverleaf structure; wobble hypothesis; anticodon; Watson–Crick pairs; non‐Watson–Crick pairs; hydrogen bond; Hoogsteen pairs; dynamics; solvation; magnesium

Figure 1.

Nomenclature and base distributions in elongator transfer RNAs. (a) The accepted nomenclature of transfer RNA molecules (Sprinzl et al., ). Variable positions are present in the dihydrouridine and variable loops. The variable loop itself forms a hairpin when long enough. Residue 0 occurs only in histidinyl‐tRNAs. Straight lines indicate secondary base pairing and broken lines unusual base pairings at the beginning or end of a helix. (b) The distribution of the four common bases at corresponding positions along the sequence in 932 sequences of elongator tRNA genes (Auffinger and Westhof, ). In single strands, the adenine region always starts at –90° from the vertical. For the variable positions that are not always occupied, the proportion of sequences where they are occupied can be evaluated starting from the outer ring. Thus, position 17 is present in less than half of the sequences and positions 45 and 46 in more than half of the sequences. In helices, the colour codes for paired residues are arranged so as to follow Watson–Crick pairings; the 5′ strand has a thin outer circle and the 3′ strand a thick outer circle.

Figure 2.

Two‐dimensional and three‐dimensional representation of the tertiary structure of elongator tRNAs. (a) Two‐dimensional representation of the tertiary structure of tRNAs, as proposed by Kim , which emphasises the two main domains and the tertiary contacts linking them. Only the secondary structure can be represented in a plane without crossing lines (in other words, mathematically, a secondary structure is equivalent to a planar graph). The representation of a three‐dimensional structure and of the underlying tertiary contacts can be drawn in a plane, but with several line crossings. Such schematic drawings are, however, useful for quick assessment and comparisons of tertiary contacts. The Kim representation shows clearly the two domains, the contacts between the T and D loops and the tertiary base pairs and triples between the single‐stranded segments and the D hairpin. The contacts represented correspond to those of yeast tRNAAsp (Westhof et al., ). (b) Stereoview of a schematised representation of the tertiary structure of yeast tRNAAsp. The sugar–phosphate backbone is drawn as a ribbon and the base pairs as rods. The colour code is the same as in Figure a. Notice the characteristic deep and shallow grooves of an RNA helix in the acceptor and thymine helices, respectively.

Figure 3.

Atomic representations of the tertiary contacts in elongator tRNAs. (a) Tertiary interactions between bases as observed in yeast tRNAAsp. From top to bottom: the two trans Watson–Crick/Hoogsteen pairs T54•A58 and U8•A14; the trans Watson–Crick/Watson–Crick pair A15•U48; the cis Watson–Crick/Watson–Crick G•A pair (also called imino G•A pair); the standard cis Watson–Crick/Watson–Crick G19C56 base pair; the two unusual bifurcated pairs G18•Ψ55 and Ψ32•C38. (b) The tertiary triple contacts present in yeast tRNAAsp. The colour code is the same as in Figure a. In green, the G45…G10•U25 triple in which the amino N2 group of G45 hydrogen bonds to the Hoogsteen edge of G10 (N7 and O6). In orange, the U12–A23…A9 triple which includes a trans symmetric Hoogsteen/Hoogsteen A•A pair. In red, the Ψ13•G22…A46 triple. Notice how, in G10•U25 and Ψ13•G22, the pyrimidine base protrudes into the deep groove. The base A46 is most probably protonated in order to form a (G22)O6…H1‐N1(A46+) hydrogen bond stabilising the base triple.

Figure 4.

Sequence comparison of the 33 sequences of aspartic acid specific tRNAs available in 2000. The disposition and colour codes emphasise the structural alignment. Identical colour codes emphasise observed covariations. The sequence of the yeast tRNAAsp, illustrated in Figure and Figure , is boxed. The consensus sequence, which reflects the most frequent base at each position, is shown at the bottom. Because of the small number of sequences, this comparison gives only a glimpse of the possible base variations.

Figure 5.

Two examples of triples implicating a sheared R•R pair. In the structure of the class I yeast tRNAGln complexed with its cognate synthetase (Rould et al., ), the sheared trans Hoogsteen/Sugar‐edge A13•A22 forms a trans Watson–Crick contact with A46 (both strands are parallel). Notice the contact between the C2‐H group of A13 and the N7 of A22 marked by a lightly dotted line. Notice also in both triples, the hydrogen bond between the hydroxyl O2′ atom of the ribose of R13 with the amino N6 of A22. In the structure of the class II yeast tRNASer (Biou et al., ), the sheared G13•A22 pair forms a trans Watson–Crick/Hoogsteen contact with G9 (both strands are antiparallel). Notice the hydrogen bond between the N1(G9) and an anionic phosphate oxygen of A22.

Figure 6.

Structural adaptation of tRNAs. (a) Structural alignment of tRNA from five different crystal structures (see PDB codes): 1TRNA, tRNAPhe (red); 2FMT, tRNAfMet (orange); 1F7U, tRNAArg in complex with class I ArgRS (yellow), 1C0A, tRNAAsp in complex with class I AspRS (green); 3FOZ, tRNAPhe in complex with isopentenyl‐tRNA transferase (blue); 2WRQ, tRNAThr in complex with EF‐Tu at the ribosomal A/T site (purple). From Alexander et al.. Reproduced by permission of Elsevier. (b) Ribbon model and secondary structure of the λ‐form of tRNAVal bound to archaeosine tRNA‐guanine transglycosylase (ArcTGT). The nucleotide residues in the protruded D arm and DV helix are coloured red. From Ishitani et al.. Reproduced by permission of Elsevier. (c) Distorsion of aminoacyl‐tRNA in the A/T state. A comparison of the A/T tRNA (purple) with the fully accommodated canonical A/A tRNA (dark blue) shows the overall extend of tRNA distorsion. From Schmeing et al.. Reproduced by permission of American Association for the Advancement of Science.

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Westhof, Eric, and Auffinger, Pascal(Jun 2012) Transfer RNA Structure. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000527.pub2]