RNA Structure: Tetraloops

Ribonucleic acid (RNA) hairpins are among the most common RNA secondary structural elements that are frequently capped by tetraloops. An RNA tetraloop structure is composed of a Watson–Crick base-paired stem and four loop nucleotides. The structure is compact and stable. The first and the fourth nucleotides form a base pair in most of the tetraloops, leaving two unpaired nucleotides in the loop. A sharp turn in the backbone is stabilized by ribose–base, base–phosphate hydrogen bonds and base stacking interactions. Tetraloops help in the folding of RNA by initiating the process. Additionally, they provide sites for RNA tertiary contacts and for protein binding, facilitating the assembly of ribonucleoprotein particles. Certain interactions, some of which are sequence-specific and others structure-specific, can be involved in the recognition of tetraloops by proteins and RNAs.

Key concepts:

  • RNA hairpins play important structural and functional roles in RNA.
  • Tetraloops help the folding of RNA and provide sites for RNA–RNA and RNA–protein interactions.
  • U turn motif, a sharp backbone turn in tetraloops, is stabilized by ribose–base, base–phosphate hydrogen bonds and base stacking interactions.

Keywords: RNA structure; tetraloop; hairpin; loop structure; mini-loop

Figure 1. Hydrogen bonds found in tetraloop structures. (a) and (b) Watson–Crick and (c) GU wobble base pairs drawn for comparison. (d) Bifurcated hydrogen bond between the first U and the fourth G in UUCG tetraloop. (e) Sheared base pair found in GNRA tetraloops. (f) G·A mismatch found in the GNRN-like structure of the AMP–aptamer complex. (g)–(i) Ribose–base hydrogen bonds. The hydrogen bonds between 2¢-OH of the first U and O6 of the fourth G in UUCG (g) and between 2¢-OH of the first G and N7 of the third A in GCAA (h) tetraloops stabilize the backbone turn. The amino group of the fourth A and O2¢ of the first G also makes a hydrogen bond in the GCAA (i) tetraloop. (j) Ribose–phosphate hydrogen bond found in the UGAA tetraloop. (k)–(n) Base–phosphate hydrogen bonds found in the UUCG (k), GNRA (l) and (m) and UGAA (n) tetraloops.
Figure 2. UUCG (a) and GCAA (b) tetraloop structures. Hydrogen bonds are shown as dotted green lines. Carbon atoms are shown in green, phosphorus purple, nitrogen blue, oxygen red and hydrogen white.
Figure 3. U turn motif in a GAAA tetraloop. The backbone turn occurs at the GpA step and the turn is stabilized by a ribose–base (2¢-OH of the first G and N7 of the fourth A) and a base–phosphate (amino proton of the first G and phosphate of the fourth A) hydrogen bonds. Carbon atoms are shown in green, phosphorus purple, nitrogen blue, oxygen red and hydrogen white.
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    book Nagai K and Mattaj IW (1995) RNA–Protein Interactions. Oxford: Oxford University Press.
    Xin Y, Laing C, Leontis NB and Schlick T (2008) Annotation of tertiary interactions in RNA structures reveals variations and correlations. RNA 14: 2465–2477.
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Cheong, Chaejoon, and Cheong, Hae‐Kap(Feb 2010) RNA Structure: Tetraloops. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003135.pub2]