RNA Structure: Pseudoknots

Abstract

An RNA pseudoknot results from Watson–Crick base pairing of a single‐stranded segment, located between two regions, paired to each other, with a sequence that is not located between these paired regions. This leads to a structure with at least two helical stems and two loops crossing the grooves of the helices. Pseudoknots are further stabilised by coaxial stacking between stems and the formation of triple ribonucleic acid (RNA) interactions between stems and loops. RNA pseudoknots adopt different folding topologies and are an essential part of various functional RNA molecules, including ribosomal RNAs, ribozymes and riboswitches. In this review, the thermodynamics and main structural features of pseudoknots, important for their function, are discussed: amongst others, viral tRNA‐like structures, ribosomal frameshifter pseudoknots and pseudoknots formed by S‐adenosylmethionine and pre‐queuosine riboswitches upon binding of their respective ligands. Key Concepts: The simplest RNA pseudoknot is formed by base‐pairing of nucleotides within a hairpin loop to a complementary sequence outside the hairpin (H‐pseudoknot). Classical H‐pseudoknots consist of two coaxially stacked helical stems and two loops that cross one deep groove of one helix and the shallow groove of the other helical stem. Pseudoknots are usually stabilised by coaxial stacking between stems and triple base pairs formed between the bases of the stems and loops. Many complex pseudoknots may be interpreted as classical pseudoknots containing additional structural elements inserted in the pseudoknot loops. Pseudoknots are folded in various types of RNA molecules and have diverse functions. Limited information is available on thermodynamic stability of pseudoknots. Computer‐assisted prediction of pseudoknots is partially hampered by a lack of knowledge about the thermodynamics of pseudoknot folding.

Molecular knots in biology and chemistry

“…Prediction of the structure of pseudoknots in RNA has rapidly developed over recent years, and, although it is still challenging for very long sequences, a number of different approaches can be used which are increasing in speed and accuracy. Interested readers are directed towards the following references for a more detailed discussion of all of these topics [10,11,14,63,68,69]. It is interesting to note that RNA sequences have been designed to form a synthetic trefoil knot [132], see Discussion for further details.…”

“…Recently, the importance and prevalence of knots at a molecular level have become truly apparent and this has attracted increasing interest from scientists in different fields. In nature, molecular knots (including slipknots and pseudoknots) are found throughout biology and exist in three major classes of biopolymers: DNA, RNA and proteins [7][8][9][10][11][12][13][14][15]. Although it is still unclear as to whether these complex topologies are evolutionary advantageous, most natural knots are thought to play a significant role in the structural, dynamic and/or functional properties of the biological systems they are associated with.…”

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

“…41,[52][53][54][55]59,61 The description of the RNA formal structures is completed by pseudoknots that result from (canonical) base pairing between a hairpin loop (or another secondary structure element) and a single distal complementary strand region. 64 In topological terms, pseudoknot formation produces a long base-paired double helix, formed by the combination of two base-paired double helices, where one of the strands is continuous and the other is discontinuous, and two loops that embed the helix within the complete continuous sequence (Figure 4B). Note that by discontinuous strand we mean that the strand lacks continuous covalent bonding along the helix.…”

An RNA pseudoknot is essential for standby-mediated translation of thetisBtoxin mRNA inEscherichia coli

“…The most prevalent pseudoknot, denoted H-type, displays co-axial stacking of two stem regions (Figure 1B ; stems S1 and S2), connected by three loop regions (Figure 1B ; L1, L2, and L3) ( 30–32 ). These RNA structure elements are often critical for regulation of gene expression in viruses, pro-, and eukaryotes ( 33 , 34 ). Pseudoknots are structurally diverse, differing in topology due to variations in the length of the loops and helices that they are built from ( 31 , 32 , 35 ).…”