RNA Structure: Tetraloops

Abstract

RNA hairpins are among the most common RNA secondary structural elements and are frequently capped by RNA tetraloops. RNA tetraloops are composed of characteristic four‐loop nucleotides that form a compact and stable structure. While they can be formed by many different nucleotide sequences, UNCG (N = A, C, G, or U), GNRA (R = A or G), and CUUG tetraloops are found most often. Tetraloops usually help initiate RNA‐folding processes and provide sites for tertiary contacts within or between RNAs and for protein binding, thereby facilitating the assembly of ribonucleoprotein particles. Tetraloop interactions can be either sequence‐ or structure‐specific. Herein, we discuss the structures of RNA tetraloops and their interactions with other RNA structural motifs and with RNA‐binding proteins.

Key Concepts

  • RNA hairpins play important structural and functional roles in RNA.
  • RNA tetraloops are composed of four‐loop nucleotides that form a compact and stable structure.
  • Tetraloops assist RNA folding and provide sites for RNA–RNA and RNA–protein interactions.
  • Tetraloop interactions can be either sequence‐ or structure‐specific.
  • We discuss the structures of RNA tetraloops and their interactions with other RNAs and proteins.

Keywords: tetraloop; hairpin; RNA structure; RNA–RNA interaction; RNA–protein interaction

Figure 1. UUCG (PDB ID: 2KOC) (a) and GCAA (PDB ID: 1ZIH) (b) tetraloop structures. Hydrogen bonds are shown as dotted black lines. Carbon atoms are shown in green, phosphorus in purple, nitrogen in blue, oxygen in red, and hydrogen in white.
Figure 2. (a, b) Close stereo‐view of the NMR structure of GAAA tetraloop/11‐nt receptor (PDB ID: 2I7Z). A, U, G, and C are shown in yellow, green, blue, and red, respectively.
Figure 3. The tertiary interactions between tetraloop and its receptor identified in large RNA molecules. (a) a GAAA–11 nt interaction in the P4–P6 domain of Tetrahymena Group I intron (PDB ID: 1GID), (b) a GCGA from stem IC docks to UU‐AG base pair in DII (left‐bottom), and a GAAC tetraloop from DV interacts with the UGA bulge in ID1 (middle), of Group II intron from Oceanobacillus iheyensis (PDB ID: 3BWP), (c) a GAAA tetraloop from P2 interacts with 10‐nt receptor from P3 shown in class I c‐di‐GMP riboswitch from Vibrio Cholerae (PDB ID: 3IRW). The tetraloop and receptor are indicated in blue and red, respectively.
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Further Reading

Ishikawa J, Fujita Y, Maeda Y, Furuta H and Ikawa Y (2011) GNRA/receptor interacting modules: versatile modular units for natural and artificial RNA architectures. Methods 54: 226–38. 10.1016/j.ymeth.2010.12.011. Review. PMID:21163353

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Thapar R, Denmon AP and Nikonowicz EP (2014) Recognition modes of RNA tetraloops and tetraloop‐like motifs by RNA‐binding proteins. Wiley Interdisciplinary Reviews. RNA 5: 49–67. 10.1002/wrna.1196. Review. PMID:24124096

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Cheong, Hae‐Kap, Kim, Nak‐Kyoon, and Cheong, Chaejoon(Feb 2015) RNA Structure: Tetraloops. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003135.pub3]