Regulatory effects of cotranscriptional RNA structure formation and transitions

2016 ◽  
Vol 7 (5) ◽  
pp. 562-574 ◽  
Author(s):  
Sheng-Rui Liu ◽  
Chun-Gen Hu ◽  
Jin-Zhi Zhang
Keyword(s):  
Structure Formation ◽  
Rna Structure ◽  
Regulatory Effects

scholarly journals CoBold: a method for identifying different functional classes of transient RNA structure features that can impact RNA structure formation in vivo

2020 ◽  
Author(s):  
Adrián López Martín ◽  
Mohamed Mounir ◽  
Irmtraud M Meyer
Keyword(s):  
Structure Formation ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Computational Method ◽  
Data Visualisation ◽  
Multiple Sequence ◽  
Functional Roles ◽  
Functional Classes ◽  
The Given

Abstract RNA structure formation in vivo happens co-transcriptionally while the transcript is being made. The corresponding co-transcriptional folding pathway typically involves transient RNA structure features that are not part of the final, functional RNA structure. These transient features can play important functional roles of their own and also influence the formation of the final RNA structure in vivo. We here present CoBold, a computational method for identifying different functional classes of transient RNA structure features that can either aid or hinder the formation of a known reference RNA structure. Our method takes as input either a single RNA or a corresponding multiple-sequence alignment as well as a known reference RNA secondary structure and identifies different classes of transient RNA structure features that could aid or prevent the formation of the given RNA structure. We make CoBold available via a web-server which includes dedicated data visualisation.

scholarly journals Prebiotically-relevant low polyion multivalency can improve functionality of membraneless compartments

2020 ◽  
Author(s):  
Fatma Pir Cakmak ◽  
Saehyun Choi ◽  
McCauley O. Meyer ◽  
Philip C. Bevilacqua ◽  
Christine D. Keating
Keyword(s):  
Molecular Weight ◽  
Phase Separation ◽  
Structure Formation ◽  
Rna Structure ◽  
Salt Resistance ◽  
Origins Of Life ◽  
Complex Coacervation ◽  
The Impact ◽  
Local Ph

AbstractMultivalent polyions can undergo complex coacervation, producing membraneless compartments that accumulate ribozymes and enhance catalysis, and offering a mechanism for functional prebiotic compartmentalization in the origins of life. Here, we evaluated the impact of low, prebiotically-relevant polyion multivalency in coacervate performance as functional compartments. As model polyions, we used positively and negatively charged homopeptides with one to 100 residues, and adenosine mono-, di-, and triphosphate nucleotides. Polycation/polyanion pairs were tested for coacervation, and resulting membraneless compartments were analyzed for salt resistance, ability to provide a distinct internal microenvironment (apparent local pH, RNA partitioning), and effect on RNA structure formation. We find that coacervates formed by phase separation of the relatively shorter polyions more effectively generated distinct pH microenvironments, accumulated RNA, and preserved duplexes. Hence, reduced multivalency polyions are not only viable as functional compartments for prebiotic chemistries, but they can offer advantages over higher molecular weight analogues.

scholarly journals Prebiotically-relevant low polyion multivalency can improve functionality of membraneless compartments

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatma Pir Cakmak ◽  
Saehyun Choi ◽  
McCauley O. Meyer ◽  
Philip C. Bevilacqua ◽  
Christine D. Keating
Keyword(s):  
Molecular Weight ◽  
Phase Separation ◽  
Structure Formation ◽  
Rna Structure ◽  
Functional Performance ◽  
Salt Resistance ◽  
Origins Of Life ◽  
Complex Coacervation ◽  
The Impact ◽  
Local Ph

AbstractMultivalent polyions can undergo complex coacervation, producing membraneless compartments that accumulate ribozymes and enhance catalysis, and offering a mechanism for functional prebiotic compartmentalization in the origins of life. Here, we evaluate the impact of lower, more prebiotically-relevant, polyion multivalency on the functional performance of coacervates as compartments. Positively and negatively charged homopeptides with 1–100 residues and adenosine mono-, di-, and triphosphate nucleotides are used as model polyions. Polycation/polyanion pairs are tested for coacervation, and resulting membraneless compartments are analyzed for salt resistance, ability to provide a distinct internal microenvironment (apparent local pH, RNA partitioning), and effect on RNA structure formation. We find that coacervates formed by phase separation of the shorter polyions more effectively generated distinct pH microenvironments, accumulated RNA, and preserved duplexes than those formed by longer polyions. Hence, coacervates formed by reduced multivalency polyions are not only viable as functional compartments for prebiotic chemistries, they can outperform higher molecular weight analogues.

scholarly journals Cotranscriptional kinetic folding of RNA secondary structures

2020 ◽  
Author(s):  
Vo Hong Thanh ◽  
Pekka Orponen
Keyword(s):  
Structure Formation ◽  
Rna Structure ◽  
Rna Folding ◽  
Computational Prediction ◽  
Simulation Method ◽  
Rna Structures ◽  
Rna Molecules ◽  
Primitive Operation ◽  
Nucleotide Resolution ◽  
Kinetics Of

Computational prediction of RNA structures is an important problem in computational structural biology. Studies of RNA structure formation often assume that the process starts from a fully synthesized sequence. Experimental evidence, however, has shown that RNA folds concurrently with its elongation. We investigate RNA structure formation, taking into account also the cotranscriptional effects. We propose a single-nucleotide resolution kinetic model of the folding process of RNA molecules, where the polymerase-driven elongation of an RNA strand by a new nucleotide is included as a primitive operation, together with a stochastic simulation method that implements this folding concurrently with the transcriptional synthesis. Numerical case studies show that our cotranscriptional RNA folding model can predict the formation of metastable conformations that are favored in actual biological systems. Our new computational tool can thus provide quantitative predictions and offer useful insights into the kinetics of RNA folding.

scholarly journals Impact of virus subtype and host IFNL4 genotype on large-scale RNA structure formation in the genome of hepatitis C virus

RNA ◽  
2020 ◽  
Vol 26 (11) ◽  
pp. 1541-1556 ◽  
Author(s):  
Peter Simmonds ◽  
Lize Cuypers ◽  
Will L. Irving ◽  
John McLauchlan ◽  
Graham S. Cooke ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structure Formation ◽  
Rna Structure ◽  
Large Scale ◽  
Virus Subtype

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 On the importance of cotranscriptional RNA structure formation

RNA ◽  
2013 ◽  
Vol 19 (11) ◽  
pp. 1461-1473 ◽  
Author(s):  
D. Lai ◽  
J. R. Proctor ◽  
I. M. Meyer
Keyword(s):  
Structure Formation ◽  
Rna Structure

scholarly journals RNA polymerase pausing and nascent-RNA structure formation are linked through clamp-domain movement

2014 ◽  
Vol 21 (9) ◽  
pp. 794-802 ◽  
Author(s):  
Pyae P Hein ◽  
Kellie E Kolb ◽  
Tricia Windgassen ◽  
Michael J Bellecourt ◽  
Seth A Darst ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Structure Formation ◽  
Rna Structure ◽  
Domain Movement ◽  
Nascent Rna ◽  
Polymerase Pausing

The Role of Zinc in Thyroid Hormones Metabolism

2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Scientific Evidence ◽  
Thyroid Stimulating Hormone ◽  
Zinc Transporters ◽  
Serum Concentrations ◽  
Metabolic Adaptations ◽  
Serum T3 ◽  
Regulatory Effects ◽  
Shed Light

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.

Sign in / Sign up

Export Citation Format

Share Document