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.

Directed Evolution of 2′-Fluoro-Modified, RNA-Supported Carbohydrate Clusters That Bind Tightly to HIV Antibody 2G12

“…Three of the four glycans in 15F3 reside near the end of a stem or in a GNRA tetraloop (specifically GUGA), which is a common natural RNA folding motif . Although this fold has not, to our knowledge, been reported in 2′-fluoro-pyrimidine aptamers, the major hydrogen bonding interactions that confer stability to the tetraloop are all between the purines at the first, third, and fourth positions, with base stacking contributing to stability between the 2–4 bases in the loop in some variations . Therefore, the 2′-fluoro uridine could reasonably be accommodated in the canonical GNRA structure (SI Figure 13).…”

The effect of Dicer knockout on RNA interference using various Dicer substrate interfering RNA structures

“…RNA hairpins play essential structural and functional roles by providing sites for RNA tertiary contacts and protein binding, which facilitates the assembly of ribonucleoprotein particles. More than half of all known RNA hairpins are composed of four nucleotides, called tetra-loops (1)(2)(3)(4)(5). Consequently, RNA tetra-loops are predominant and are commonly found in nature.…”

Independent evolution of tetraloop in enterovirus oriL replicative element and its putative binding partners in virus protein 3C

“…The apical loops of domain d in genomes belonging to several viruses of Enterovirus genera were shown by NMR experiments to be tetraloops with a specific spatial structure, which belongs to the UNCG structural class of stable tetraloops ( Du et al, 2003 ; Du et al, 2004 ; Ihle et al, 2005 ; Melchers et al, 2006 ). There are several known structural classes of tetraloops, three of which, named according to consensus sequences, contain tetraloops of extreme stability: UNCG (where N = any nucleotide), GNRA (where R = A/G) and gCUUGc ( Uhlenbeck, 1990 ; Cheong & Cheong, 2010 ). Tetraloops of UNCG and GNRA classes are the most widely represented ( Woese et al, 1990 ; Cheong & Cheong, 2010 ; Bottaro & Lindorff-Larsen, 2017 ).…”

“…There are several known structural classes of tetraloops, three of which, named according to consensus sequences, contain tetraloops of extreme stability: UNCG (where N = any nucleotide), GNRA (where R = A/G) and gCUUGc ( Uhlenbeck, 1990 ; Cheong & Cheong, 2010 ). Tetraloops of UNCG and GNRA classes are the most widely represented ( Woese et al, 1990 ; Cheong & Cheong, 2010 ; Bottaro & Lindorff-Larsen, 2017 ). Previously, it was shown that only tetraloops of the UNCG structural class, but not tetraloops of GNRA or gCUUGc structural classes, can support effective replication of the poliovirus genome ( Prostova et al, 2015 ).…”