Dataset Information

Out of balance: R-loops in human disease.

ABSTRACT: R-loops are cellular structures composed of an RNA/DNA hybrid, which is formed when the RNA hybridises to a complementary DNA strand and a displaced single-stranded DNA. R-loops have been detected in various organisms from bacteria to mammals and play crucial roles in regulating gene expression, DNA and histone modifications, immunoglobulin class switch recombination, DNA replication, and genome stability. Recent evidence suggests that R-loops are also involved in molecular mechanisms of neurological diseases and cancer. In addition, mutations in factors implicated in R-loop biology, such as RNase H and SETX (senataxin), lead to devastating human neurodegenerative disorders, highlighting the importance of correctly regulating the level of R-loops in human cells. In this review we summarise current advances in this field, with a particular focus on diseases associated with dysregulation of R-loop structures. We also discuss potential therapeutic approaches for such diseases and highlight future research directions.

SUBMITTER: Groh M

PROVIDER: S-EPMC4169248 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Out of balance: R-loops in human disease.

Groh Matthias M Gromak Natalia N

PLoS genetics 20140918 9

R-loops are cellular structures composed of an RNA/DNA hybrid, which is formed when the RNA hybridises to a complementary DNA strand and a displaced single-stranded DNA. R-loops have been detected in various organisms from bacteria to mammals and play crucial roles in regulating gene expression, DNA and histone modifications, immunoglobulin class switch recombination, DNA replication, and genome stability. Recent evidence suggests that R-loops are also involved in molecular mechanisms of neurolo ...[more]

PMID: 25233079

Similar Datasets

Project description:ObjectiveTo assess the effect of exercise training by using the Nintendo Wii Fit video game and balance board system on balance and gait in adults with Parkinson disease (PD).DesignA prospective interventional cohort study.SettingAn outpatient group exercise class.ParticipantsTen subjects with PD, Hoehn and Yahr stages 2.5 or 3, with a mean age of 67.1 years; 4 men, 6 women.InterventionsThe subjects participated in supervised group exercise sessions 3 times per week for 8 weeks by practicing 3 different Wii balance board games (marble tracking, skiing, and bubble rafting) adjusted for their individualized function level. The subjects trained for 10 minutes per game, a total of 30 minutes training per session.Main outcome measurementsPre-and postexercise training, a physical therapist evaluated subjects' function by using the Berg Balance Scale, Dynamic Gait Index, and Sharpened Romberg with eyes open and closed. Postural sway was assessed at rest and with tracking tasks by using the Wii balance board. The subjects rated their confidence in balance by using the Activities-specific Balance Confidence scale and depression on the Geriatric Depression Scale.ResultsBalance as measured by the Berg Balance Scale improved significantly, with an increase of 3.3 points (P = .016). The Dynamic Gait Index improved as well (mean increase, 2.8; P = .004), as did postural sway measured with the balance board (decreased variance in stance with eyes open by 31%; P = .049). Although the Sharpened Romberg with eyes closed increased by 6.85 points and with eyes opened by 3.3 points, improvements neared significance only for eyes closed (P = .07 versus P = .188). There were no significant changes on patient ratings for the Activities-specific Balance Confidence (mean decrease, -1%; P = .922) or the Geriatric Depression Scale (mean increase, 2.2; P = .188).ConclusionsAn 8-week exercise training class by using the Wii Fit balance board improved selective measures of balance and gait in adults with PD. However, no significant changes were seen in mood or confidence regarding balance.

Project description:Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long unstructured loops are a major part of unstructured regions in molecular networks.

Dataset Information

Out of balance: R-loops in human disease.

Publications

Out of balance: R-loops in human disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets