The theory of helix-based RNA folding kinetics and its application

doi:10.1088/1674-1056/abab84

Abstract

RNAs carry out diverse biological functions, partly because different conformations of the same RNA sequence can play different roles in cellular activities. To fully understand the biological functions of RNAs requires a conceptual framework to investigate the folding kinetics of RNA molecules, instead of native structures alone. Over the past several decades, many experimental and theoretical methods have been developed to address RNA folding. The helix-based RNA folding theory is the one which uses helices as building blocks, to calculate folding kinetics of secondary structures with pseudoknots of long RNA in two different folding scenarios. Here, we will briefly review the helix-based RNA folding theory and its application in exploring regulation mechanisms of several riboswitches and self-cleavage activities of the hepatitis delta virus (HDV) ribozyme.

Keywords: RNA folding kinetics RNA structure Riboswitch HDV ribozyme

Received: 29 June 2020
Revised: 30 July 2020
Accepted manuscript online: 01 August 2020

PACS:	87.14.gn	(RNA)
	87.15.bd	(Secondary structure)
	87.15.Cc	(Folding: thermodynamics, statistical mechanics, models, and pathways)
	87.18.Cf	(Genetic switches and networks)

Corresponding Authors: ^†Corresponding author. E-mail: wbzhang@whu.edu.cn

About author:

†Corresponding author. E-mail: wbzhang@whu.edu.cn

* Project supported by the Science Fund from the Key Laboratory of Hubei Province, China (Grant No. 201932003) and the National Natural Science Foundation of China (Grant Nos. 1157324 and 31600592).

Cite this article:

Sha Gong(龚沙), Taigang Liu(刘太刚), Yanli Wang(王晏莉), and Wenbing Zhang(张文炳)† The theory of helix-based RNA folding kinetics and its application 2020 Chin. Phys. B 29 108703

Fig. 1.

Transitions between states (A, B, C) through formation (A to B), disruption (B to A) of a helix (red), and exchange between two helices in A (green) and C (the left/right shoulder of the helix is colored black/green). The relevant pathways labeled along the arrow are shown in the bottom boxes, where the dotted dark lines denote the schematic energy landscape of zipping and tunneling pathways. The unfolding-refolding pathway are shown with gray color, U is the unfolded, open chain.

Fig. 2.

The main pathways of HDV ribozyme under two different scenarios: refolding (a) and co-transcriptional folding (b). Upper and lowercase letters denote the ribozyme region and the flanking region. The unpaired nucleotides in the external loop are simply described by dotted lines in panel (a). The rate-limited transition in the slow refolding pathway panel (a) and the main co-transcriptional transition with net flux about 90% (b) are shown with red and green arrows respectively. Except the different RNA lengths in panels (a) and (b), structure model of states denoted inside and outside parentheses in panel (b) are the same.

Fig. 3.

The co-transcriptional folding behaviors of the yjdF riboswitch from B. subtilis. The population kinetics of main states and their structure at an elongation rate of 15 nt/s are shown in (a) with 0-μM and (b) with 10-μM ligand. Important folding events are mapped in the low panel. The superscript “b” denotes the corresponding state with ligand bound. C0 is the open chain and C4 is a four-way branch structure shown in box near C5. Structures C1, C2, and C3 composed of one or more hairpins labeled in the brackets nearby. The RBS region is colored pink.

Fig. 4.

Structure transitions on main co-transcriptional folding pathways of the pbuE riboswitch. T is the terminator hairpin. Nucleotides within helix regions of the aptamer structure and the pause site are colored differently.

Fig. 5.

Regulatory behaviors of the TPP (a) and S_MK riboswitch (b). The nature ligand of S_MK riboswitch is S-adenosylmethionine (SAM). The arrows with dotted lines denote the co-transcriptional folding, where RNAs transit from a series of intermediate states (not shown) to ON state, which is formed near the end of transcription. The 5’ splice site in the TPP riboswitch (a) and the SD in the S_MK riboswitch are colored red. The 5’ ends of nascent RNA are shown with red circles.

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