scholarly journals RNA tertiary structure energetics predicted by an ensemble model of the RNA double helix

2018 ◽  
Author(s):  
Joseph D. Yesselman ◽  
Sarah K. Denny ◽  
Namita Bisaria ◽  
Daniel Herschlag ◽  
William J. Greenleaf ◽  
...  
Keyword(s):  
Base Pair ◽  
Tertiary Structure ◽  
Double Helix ◽  
Structure Stability ◽  
Conformational Ensemble ◽  
Experimental Platform ◽  
Rna Tertiary Structure ◽  
Crystallographic Structures ◽  
Thermodynamic Effects ◽  
Detailed Picture

ABSTRACTOver 50% of residues within functional structured RNAs are base-paired in Watson-Crick helices, but it is not fully understood how these helices’ geometric preferences and flexibility might influence RNA tertiary structure. Here, we show experimentally and computationally that the ensemble fluctuations of RNA helices substantially impact RNA tertiary structure stability. We updated a model for the conformational ensemble of the RNA helix using crystallographic structures of Watson-Crick base pair steps. To test this model, we made blind predictions of the thermodynamic stability of >1500 tertiary assemblies with differing helical sequences and compared calculations to independent measurements from a high-throughput experimental platform. The blind predictions accounted for thermodynamic effects from changing helix sequence and length with unexpectedly tight accuracies (RMSD of 0.34 and 0.77 kcal/mol, respectively). These comparisons lead to a detailed picture of how RNA base pair steps fluctuate within complex assemblies and suggest a new route toward predicting RNA tertiary structure formation and energetics.

scholarly journals Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and their preference for a CG closing base pair

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4236
Author(s):  
Kaethe N. Leonard ◽  
Joshua M. Blose
Keyword(s):  
Secondary Structure ◽  
Base Pair ◽  
Structural Changes ◽  
Tertiary Structure ◽  
Vis Spectroscopy ◽  
Rna Tertiary Structure ◽  
The Stability ◽  
And Function ◽  
Peg 8000

Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo. To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG) 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair. The thermal denaturation of model hairpins containing GAAA loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG 200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic preference for a CG base pair by destabilizing the loop with a CG closing base pair relative to the loop with a GC closing base pair. This result also extended to a related DNA triloop, which provides further evidence that the interactions between the loop and closing base pair are identical for the d(GCA) triloop and the GAAA tetraloop. Our results suggest that in the presence of model PEG molecules, loops with a GC closing base pair may retain some preferential interactions with the cosolutes that are lost in the presence of the CG closing base pair. These results reveal that relatively small structural changes could influence how neutral cosolutes tune the stability and function of secondary structure motifs in vivo.

scholarly journals Sequence-dependent RNA helix conformational preferences predictably impact tertiary structure formation

2019 ◽  
Vol 116 (34) ◽  
pp. 16847-16855 ◽  
Author(s):  
Joseph D. Yesselman ◽  
Sarah K. Denny ◽  
Namita Bisaria ◽  
Daniel Herschlag ◽  
William J. Greenleaf ◽  
...  
Keyword(s):  
Structure Formation ◽  
Rna Structure ◽  
Tertiary Structure ◽  
Protein Translation ◽  
Detailed Comparison ◽  
Structure Stability ◽  
Control Of Gene Expression ◽  
Conformational Preferences ◽  
Rna Tertiary Structure ◽  
Length Changes

Structured RNAs and RNA complexes underlie biological processes ranging from control of gene expression to protein translation. Approximately 50% of nucleotides within known structured RNAs are folded into Watson–Crick (WC) base pairs, and sequence changes that preserve these pairs are typically assumed to preserve higher-order RNA structure and binding of macromolecule partners. Here, we report that indirect effects of the helix sequence on RNA tertiary stability are, in fact, significant but are nevertheless predictable from a simple computational model called RNAMake-∆∆G. When tested through the RNA on a massively parallel array (RNA-MaP) experimental platform, blind predictions for >1500 variants of the tectoRNA heterodimer model system achieve high accuracy (rmsd 0.34 and 0.77 kcal/mol for sequence and length changes, respectively). Detailed comparison of predictions to experiments support a microscopic picture of how helix sequence changes subtly modulate conformational fluctuations at each base-pair step, which accumulate to impact RNA tertiary structure stability. Our study reveals a previously overlooked phenomenon in RNA structure formation and provides a framework of computation and experiment for understanding helix conformational preferences and their impact across biological RNA and RNA-protein assemblies.

scholarly journals Evidence for a Thermodynamically Distinct Mg2+Ion Associated with Formation of an RNA Tertiary Structure

2011 ◽  
Vol 133 (34) ◽  
pp. 13397-13405 ◽  
Author(s):  
Desirae Leipply ◽  
David E. Draper
Keyword(s):  
Tertiary Structure ◽  
Rna Tertiary Structure

scholarly journals Studies of Transfer RNA Tertiary Structure by Singlet-Singlet Energy Transfer

1974 ◽  
Vol 71 (7) ◽  
pp. 2838-2842 ◽  
Author(s):  
C.-H. Yang ◽  
D. Soll
Keyword(s):  
Energy Transfer ◽  
Tertiary Structure ◽  
Transfer Rna ◽  
Rna Tertiary Structure
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