Dataset Information

The Story of RNA Folding, as Told in Epochs.

ABSTRACT: The past decades have witnessed tremendous developments in our understanding of RNA biology. At the core of these advances have been studies aimed at discerning RNA structure and at understanding the forces that influence the RNA folding process. It is easy to take the present state of understanding for granted, but there is much to be learned by considering the path to our current understanding, which has been tortuous, with the birth and death of models, the adaptation of experimental tools originally developed for characterization of protein structure and catalysis, and the development of novel tools for probing RNA. In this review we tour the stages of RNA folding studies, considering them as "epochs" that can be generalized across scientific disciplines. These epochs span from the discovery of catalytic RNA, through biophysical insights into the putative primordial RNA World, to characterization of structured RNAs, the building and testing of models, and, finally, to the development of models with the potential to yield generalizable predictive and quantitative models for RNA conformational, thermodynamic, and kinetic behavior. We hope that this accounting will aid others as they navigate the many fascinating questions about RNA and its roles in biology, in the past, present, and future.

SUBMITTER: Herschlag D

PROVIDER: S-EPMC6169817 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Story of RNA Folding, as Told in Epochs.

Herschlag Daniel D Bonilla Steve S Bisaria Namita N

Cold Spring Harbor perspectives in biology 20181001 10

The past decades have witnessed tremendous developments in our understanding of RNA biology. At the core of these advances have been studies aimed at discerning RNA structure and at understanding the forces that influence the RNA folding process. It is easy to take the present state of understanding for granted, but there is much to be learned by considering the path to our current understanding, which has been tortuous, with the birth and death of models, the adaptation of experimental tools or ...[more]

PMID: 30275276

Similar Datasets

Project description:BackgroundMedical educators have promoted self-directed learning (SDL) as an important means of enabling students to take responsibility for their own learning throughout their training and practice. While SDL has been well-studied in classroom settings, it remains a story half told: barriers to and facilitators of SDL in the clinical setting are not yet well described. The goals of this study were to explicate student experiences of SDL in their clinical training and to identify the roles that local social and cultural contexts play in shaping their experiences of SDL.MethodsTo understand students' conceptualization and experiences of SDL in the clinical setting, we carried out a qualitative study with 15 medical students at Harvard Medical School. The semi-structured interviews were recorded and transcribed. Using an interpretivist approach, data were analyzed both deductively and inductively using the Framework method of content analysis.ResultsParticipants described patient care activities as primary motivators for engagement in SDL in the clinical setting. Participants' descriptions of SDL aligned with Knowles' steps in SDL, with an additional step of consolidation of learning related to their patients' diagnosis and management. Participants described using a range of cognitive, social-emotional, and peer learning strategies to enhance their SDL. Participants who described a growth mindset appeared to engage in SDL more easily. Learning environments that fostered SDL were those in which faculty and residents demonstrated an educational orientation, promoted psychological safety, and invited student engagement. Teams with perceived excessive work demands were perceived to be less supportive of SDL.ConclusionsOur study enhances previous classroom-based models of SDL by providing specific, practical implications for both students and faculty in the clinical training setting. Participants described SDL in the clinical setting as patient-centered, and when effectively implemented, SDL appears to support a mastery rather than performance orientation. Our study paves the way for improving medical students' clinical SDL and helping them become lifelong learners in the field of medicine.

Project description:BACKGROUND:In the animal production sector, enteritis is responsible for serious economic losses, and intestinal parasitism is a major stress factor leading to malnutrition and lowered performance and animal production efficiency. The effect of enteric parasites on the gut function of teleost fish, which represent the most ancient bony vertebrates, is far from being understood. The intestinal myxozoan parasite Enteromyxum leei dwells between gut epithelial cells and causes severe enteritis in gilthead sea bream (Sparus aurata), anorexia, cachexia, growth impairment, reduced marketability and increased mortality. METHODS:This study aimed to outline the gut failure in this fish-parasite model using a multifaceted approach and to find and validate non-lethal serum markers of gut barrier dysfunction. Intestinal integrity was studied in parasitized and non-parasitized fish by immunohistochemistry with specific markers for cellular adhesion (E-cadherin) and tight junctions (Tjp1 and Cldn3) and by functional studies of permeability (oral administration of FITC-dextran) and electrophysiology (Ussing chambers). Serum samples from parasitized and non-parasitized fish were analyzed using non-targeted metabolomics and some significantly altered metabolites were selected to be validated using commercial kits. RESULTS:The immunodetection of Tjp1 and Cldn3 was significantly lower in the intestine of parasitized fish, while no strong differences were found in E-cadherin. Parasitized fish showed a significant increase in paracellular uptake measured by FITC-dextran detection in serum. Electrophysiology showed a decrease in transepithelial resistance in infected animals, which showed a diarrheic profile. Serum metabolomics revealed 3702 ions, from which the differential expression of 20 identified compounds significantly separated control from infected groups in multivariate analyses. Of these compounds, serum inosine (decreased) and creatine (increased) were identified as relevant and validated with commercial kits. CONCLUSIONS:The results demonstrate the disruption of tight junctions and the loss of gut barrier function, a metabolomic profile of absorption dysfunction and anorexia, which further outline the pathophysiological effects of E. leei.

Project description:MotivationThe function of an RNA molecule is not only linked to its native structure, which is usually taken to be the ground state of its folding landscape, but also in many cases crucially depends on the details of the folding pathways such as stable folding intermediates or the timing of the folding process itself. To model and understand these processes, it is necessary to go beyond ground state structures. The study of rugged RNA folding landscapes holds the key to answer these questions. Efficient coarse-graining methods are required to reduce the intractably vast energy landscapes into condensed representations such as barrier trees or basin hopping graphs : BHG) that convey an approximate but comprehensive picture of the folding kinetics. So far, exact and heuristic coarse-graining methods have been mostly restricted to the pseudoknot-free secondary structures. Pseudoknots, which are common motifs and have been repeatedly hypothesized to play an important role in guiding folding trajectories, were usually excluded.ResultsWe generalize the BHG framework to include pseudoknotted RNA structures and systematically study the differences in predicted folding behavior depending on whether pseudoknotted structures are allowed to occur as folding intermediates or not. We observe that RNAs with pseudoknotted ground state structures tend to have more pseudoknotted folding intermediates than RNAs with pseudoknot-free ground state structures. The occurrence and influence of pseudoknotted intermediates on the folding pathway, however, appear to depend very strongly on the individual RNAs so that no general rule can be inferred.Availability and implementationThe algorithms described here are implemented in C++ as standalone programs. Its source code and Supplemental material can be freely downloaded from http://www.tbi.univie.ac.at/bhg.html.Contactqin@bioinf.uni-leipzig.deSupplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

The Story of RNA Folding, as Told in Epochs.

Publications

The Story of RNA Folding, as Told in Epochs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets