scholarly journals Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure

2021 ◽  
Vol 7 (4) ◽  
pp. 71
Author(s):  
Grégoire De Bisschop ◽  
Delphine Allouche ◽  
Elisa Frezza ◽  
Benoît Masquida ◽  
Yann Ponty ◽  
...  
Keyword(s):  
Rna Structure ◽  
Computational Prediction ◽  
Structure Modeling ◽  
Rna Structures ◽  
Sequencing Data ◽  
Base Pairs ◽  
Dynamic Simulations ◽  
Automated Modeling ◽  
Modeling Software ◽  
Increasing Temperature

As more sequencing data accumulate and novel puzzling genetic regulations are discovered, the need for accurate automated modeling of RNA structure increases. RNA structure modeling from chemical probing experiments has made tremendous progress, however accurately predicting large RNA structures is still challenging for several reasons: RNA are inherently flexible and often adopt many energetically similar structures, which are not reliably distinguished by the available, incomplete thermodynamic model. Moreover, computationally, the problem is aggravated by the relevance of pseudoknots and non-canonical base pairs, which are hardly predicted efficiently. To identify nucleotides involved in pseudoknots and non-canonical interactions, we scrutinized the SHAPE reactivity of each nucleotide of the 188 nt long lariat-capping ribozyme under multiple conditions. Reactivities analyzed in the light of the X-ray structure were shown to report accurately the nucleotide status. Those that seemed paradoxical were rationalized by the nucleotide behavior along molecular dynamic simulations. We show that valuable information on intricate interactions can be deduced from probing with different reagents, and in the presence or absence of Mg2+. Furthermore, probing at increasing temperature was remarkably efficient at pointing to non-canonical interactions and pseudoknot pairings. The possibilities of following such strategies to inform structure modeling software are discussed.

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 RNA secondary structure prediction using an ensemble of two-dimensional deep neural networks and transfer learning

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jaswinder Singh ◽  
Jack Hanson ◽  
Kuldip Paliwal ◽  
Yaoqi Zhou
Keyword(s):  
Secondary Structure ◽  
Transfer Learning ◽  
Rna Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Noncoding Rnas ◽  
Rna Structures ◽  
Base Pairs ◽  
Functional Annotations ◽  
Model Training

AbstractThe majority of our human genome transcribes into noncoding RNAs with unknown structures and functions. Obtaining functional clues for noncoding RNAs requires accurate base-pairing or secondary-structure prediction. However, the performance of such predictions by current folding-based algorithms has been stagnated for more than a decade. Here, we propose the use of deep contextual learning for base-pair prediction including those noncanonical and non-nested (pseudoknot) base pairs stabilized by tertiary interactions. Since only $$<$$<250 nonredundant, high-resolution RNA structures are available for model training, we utilize transfer learning from a model initially trained with a recent high-quality bpRNA dataset of $$> $$>10,000 nonredundant RNAs made available through comparative analysis. The resulting method achieves large, statistically significant improvement in predicting all base pairs, noncanonical and non-nested base pairs in particular. The proposed method (SPOT-RNA), with a freely available server and standalone software, should be useful for improving RNA structure modeling, sequence alignment, and functional annotations.

Fluorescent ribonucleoside analogues as probes for investigating RNA structure and function

2010 ◽  
Vol 83 (1) ◽  
pp. 213-232 ◽  
Author(s):  
Seergazhi G. Srivatsan ◽  
Anupam A. Sawant
Keyword(s):  
Nucleic Acid ◽  
Conformational Changes ◽  
Rna Structure ◽  
Photophysical Properties ◽  
Local Environment ◽  
Spectroscopic Techniques ◽  
Rna Structures ◽  
Base Pairs ◽  
Target Nucleic Acid ◽  
And Function

Numerous biophysical tools based on fluorescence have been developed to advance the understanding of RNA–nucleic acid, RNA–protein, and RNA–small molecule inter-actions. In this regard, fluorescent ribonucleoside analogues that are sensitive to their local environment provide sensitive probes for investigating RNA structure, dynamics, and recognition. Most of these analogues closely resemble the native ribonucleosides with respect to their overall dimension and have the ability to form canonical Watson–Crick (WC) base pairs. Therefore, it is possible to place these probes near the point of interaction in a target nucleic acid with minimum structural perturbations and gain insight into the intricacies of conformational changes taking place in and around the interaction site. Here, we provide a concise background on the development and recent advances in the applications of base-modified fluorescent ribonucleoside analogue probes. We first present various base-modified fluorescent ribonucleoside analogues, their photophysical properties, and methods to incorporate these analogues into oligoribonucleotides. We then discuss the established spectroscopic techniques, which make use of the fluorescence properties of these emissive ribonucleoside analogues. Finally, we present the applications of base-modified fluorescent ribonucleoside analogues used as probes incorporated into oligoribonucleotides in investigating RNA structures and functions.

scholarly journals RSVdb: a comprehensive database of transcriptome RNA structure

2020 ◽  
Author(s):  
Haopeng Yu ◽  
Yi Zhang ◽  
Qing Sun ◽  
Huijie Gao ◽  
Shiheng Tao
Keyword(s):  
Rna Structure ◽  
Structure Prediction ◽  
Dimethyl Sulfate ◽  
Future Research ◽  
Rna Structures ◽  
Sequencing Data ◽  
Structure Information ◽  
Online Prediction ◽  
Experimental Treatments ◽  
Transcriptome Level

Abstract RNA fulfills a crucial regulatory role in cells by folding into a complex RNA structure. To date, a chemical compound, dimethyl sulfate (DMS), has been developed to probe the RNA structure at the transcriptome level effectively. We proposed a database, RSVdb (https://taolab.nwafu.edu.cn/rsvdb/), for the browsing and visualization of transcriptome RNA structures. RSVdb, including 626 225 RNAs with validated DMS reactivity from 178 samples in eight species, supports four main functions: information retrieval, research overview, structure prediction and resource download. Users can search for species, studies, transcripts and genes of interest; browse the quality control of sequencing data and statistical charts of RNA structure information; preview and perform online prediction of RNA structures in silico and under DMS restraint of different experimental treatments and download RNA structure data for species and studies. Together, RSVdb provides a reference for RNA structure and will support future research on the function of RNA structure at the transcriptome level.

scholarly journals RSVdb: A comprehensive database of transcriptome RNA structure

2019 ◽  
Author(s):  
Haopeng Yu ◽  
Yi Zhang ◽  
Qing Sun ◽  
Huijie Gao ◽  
Shiheng Tao
Keyword(s):  
Rna Structure ◽  
Structure Prediction ◽  
Dimethyl Sulfate ◽  
Future Research ◽  
Rna Structures ◽  
Sequencing Data ◽  
Structure Information ◽  
Online Prediction ◽  
Experimental Treatments ◽  
Transcriptome Level

ABSTRACTRNA fulfills a crucial regulatory role in cells by folding into a complex RNA structure. To date, a chemical compound, dimethyl sulfate (DMS), has been developed to effectively probe the RNA structure at the transcriptome level. We proposed a database, RSVdb (https://taolab.nwafu.edu.cn/rsvdb/), for the browsing and visualization of transcriptome RNA structures. RSVdb, including 626,225 RNAs with validated DMS reactivity from 178 samples in 8 species, supports four main functions: information retrieval, research overview, structure prediction, and resource download. Users can search for species, studies, transcripts and genes of interest; browse the quality control of sequencing data and statistical charts of RNA structure information; preview and perform online prediction of RNA structures in silico and under DMS restraint of different experimental treatments; and download RNA structure data for species and studies. Together, RSVdb provides a reference for RNA structure and will support future research on the function of RNA structure at the transcriptome level.

scholarly journals Fatgraph models of RNA structure

2017 ◽  
Vol 5 (1) ◽  
pp. 1-20
Author(s):  
Fenix Huang ◽  
Christian Reidys ◽  
Reza Rezazadegan
Keyword(s):  
Rna Structure ◽  
Minimum Free Energy ◽  
Coarse Grained ◽  
Partition Functions ◽  
Rna Structures ◽  
Base Pairs ◽  
Folding Algorithm ◽  
Inverse Folding ◽  
Fixed Structure ◽  
Context Free

Abstract In this review paper we discuss fatgraphs as a conceptual framework for RNA structures. We discuss various notions of coarse-grained RNA structures and relate them to fatgraphs.We motivate and discuss the main intuition behind the fatgraph model and showcase its applicability to canonical as well as noncanonical base pairs. Recent discoveries regarding novel recursions of pseudoknotted (pk) configurations as well as their translation into context-free grammars for pk-structures are discussed. This is shown to allow for extending the concept of partition functions of sequences w.r.t. a fixed structure having non-crossing arcs to pk-structures. We discuss minimum free energy folding of pk-structures and combine these above results outlining how to obtain an inverse folding algorithm for PK structures.

scholarly journals RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures

2021 ◽  
Vol 49 (6) ◽  
pp. 3409-3426
Author(s):  
Arancha Catalan-Moreno ◽  
Marta Cela ◽  
Pilar Menendez-Gil ◽  
Naiara Irurzun ◽  
Carlos J Caballero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rna Structure ◽  
Cold Shock ◽  
Mrna Translation ◽  
Site Directed Mutagenesis ◽  
Rna Structures ◽  
Double Stranded Rna ◽  
Ambient Temperatures ◽  
Shock Proteins ◽  
Rna Hairpin

Abstract Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.

scholarly journals Conserved long-range base pairings are associated with pre-mRNA processing of human genes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Svetlana Kalmykova ◽  
Marina Kalinina ◽  
Stepan Denisov ◽  
Alexey Mironov ◽  
Dmitry Skvortsov ◽  
...  
Keyword(s):  
Long Range ◽  
Rna Folding ◽  
Current Knowledge ◽  
Rna Structures ◽  
Base Pairs ◽  
Protein Coding ◽  
Proximity Ligation ◽  
Transcriptional Suppression ◽  
Human Genes ◽  
Cleavage And Polyadenylation

AbstractThe ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3’-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation.

scholarly journals The structure of an RNA dodecamer shows how tandem U–U base pairs increase the range of stable RNA structures and the diversity of recognition sites

Structure ◽  
1996 ◽  
Vol 4 (8) ◽  
pp. 917-930 ◽  
Author(s):  
Susan E Lietzke ◽  
Cindy L Barnes ◽  
J Andrew Berglund ◽  
Craig E Kundrot
Keyword(s):  
Rna Structures ◽  
Base Pairs ◽  
Recognition Sites
Sign in / Sign up

Export Citation Format

Share Document