R-loop accumulation has been linked to numerous diseases, such as cancers of the breast, ovary, and colon, as well as neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).
This suggested that magnesium is the link between calorie restriction and R-loop suppression.
They then showed that disrupting the magnesium transporters--or taking magnesium out of the cells' growth medium--prevented the calorie-restriction benefit of suppressing R-loop formation.
Together, these findings confirmed that magnesium is indeed the connection between calorie restriction and R-loop suppression.
A series of experiments showed that magnesium significantly prevented R-loop buildup completely independent of calorie restriction.
This is of particular relevance, provided our recent observation that tumor suppressor BRCA2 gene is involved in R-loop
prevention/resolution and that, therefore, R-loops
may represent a major potential source of tumorigenesis.
SINGAPORE, May 29, 2015 - (ACN Newswire) - Scientists from A*STAR's Bioinformatics Institute (BII) have developed an analytical model and computational tool to rapidly and accurately predict the occurrence and locations of R-loop Forming Sequences (RLFSs) in any genome or artificial nucleic acid sequences.
Scientists from BII's Genome and Gene Expression Data Analysis Division developed the Quantitative Model of R-loop Forming Sequence finder (QmRLFS-finder), making it freely available to accelerate research in this area.
It is our hope that an increased understanding of R-loop formation and functions will in turn allow us to better predict and treat various diseases.
1] "Quantitative model of R-loop forming structures reveals a novel level of RNA-DNA interactome complexity", Nucleic Acids Res.
The global team tested the R-loop
model using specially modified microscopes in which single DNA molecules are stretched in a magnetic field.
As mutations in several RNA processing factors have been shown to stabilize R-loop
formation, we propose here to investigate the link between R-loops
and co-transcriptional alternative splicing (AS) and to decipher the underlying mechanisms, a hypothesis supported by our preliminary results identifying more than 3000 splice junctions affected by decreased R-loops
upon overexpression of RNase H1.