E! Science News: Turning off small RNA http... Sciencedaily: Turning off small RNA: New... Science Index: Aptam... Science Index: Syste... Molecular fossil: Crystal structure shows how RNA, one of biology's oldest catalysts, is made. (PhysOrg.com) -- In today's world of sophisticated organisms proteins are the stars. They are the indispensible catalytic workhorses, carrying out the processes essential to life. But long, long ago ribonucleic acid (RNA) reigned supreme. Now Northwestern University researchers have produced an atomic picture that shows how two of these very old molecules interact with each other.
It is a rare glimpse of the transition from an ancient, RNA-based world to our present, protein-catalyst dominated world. The scientists are the first to show the atomic details of how ribonuclease P (RNase P) recognizes, binds and cleaves transfer RNA (tRNA). Details of the structure will be published Nov. 14 by the journal Nature. "RNA is an ancient molecule, but it is pretty sophisticated," said Alfonso Mondragón, professor of molecular biosciences in the Weinberg College of Arts and Sciences. The structure shows that once RNase P recognizes tRNA, it docks and, assisted by metal ions, cuts one chemical bond. Scientists create novel RNA repair technology. Scientists from the Florida campus of The Scripps Research Institute have identified a compound that can help repair a specific type of defect in RNA, a type of genetic material. The methods in the new study could accelerate the development of therapeutics to treat a variety of incurable diseases such as Huntington's disease, Spinocerebellar ataxia, and Kennedy disease.
The new study, published January 17, 2012 in an advance, online edition of the journal ACS Chemical Biology, describes a method to find compounds that target defective RNAs, specifically RNA that carries a structural motif known as an "expanded triplet repeat. " The triplet repeat, a series of three nucleotides repeated many more times than normal in the genetic code of affected individuals, has been associated with a variety of neurological and neuromuscular disorders. Disney and his colleagues are already hard at work to extend the lab's findings. Simpler times: Did an earlier genetic molecule predate DNA and RNA?
(PhysOrg.com) -- In the chemistry of the living world, a pair of nucleic acids—DNA and RNA—reign supreme. As carrier molecules of the genetic code, they provide all organisms with a mechanism for faithfully reproducing themselves as well as generating the myriad proteins vital to living systems. Yet according to John Chaput, a researcher at the Center for Evolutionary Medicine and Informatics, at Arizona State University’s Biodesign Institute®, it may not always have been so. Chaput and other researchers studying the first tentative flickering of life on earth have investigated various alternatives to familiar genetic molecules. These chemical candidates are attractive to those seeking to unlock the still-elusive secret of how the first life began, as primitive molecular forms may have more readily emerged during the planet’s prebiotic era. Nearly every organism on earth uses DNA to encode chunks of genetic information in genes, which are then copied into RNA.
Just the two of us: Stable dinucleotide-RNA duplexes show promise in biotechnology. (PhysOrg.com) -- Nucleic acid technology has revolutionized the field of biomedicine, as it can be effectively utilized in the diagnosis, treatment, and prevention of genetic diseases The efficacy of most oligonucleotide therapies is, however, limited as a result of the lability of oligonucleotides in biological fluids and, in particular, their poor delivery to the site of action. A Swedish team headed by R. Strömberg recently reported in the European Journal of Organic Chemistry that modification of oligonucleotides with a 2'-O-carbamoyl moiety greatly increases the stability of these compounds, which may render their use in constructs for biotechnological and therapeutic applications viable. Efficiency in the regulation of gene expression is readily achieved if turnover of the target RNA is obtained, but this can only occur if native enzymes recognize the relevant oligonucleotide complex.
Explore further: Promising agents burst through 'superbug' defenses to fight antibiotic resistance. Cancer drug cisplatin found to bind like glue in cellular RNA. An anti-cancer drug used extensively in chemotherapy binds pervasively to RNA -- up to 20-fold more than it does to DNA, a surprise finding that suggests new targeting approaches might be useful, according to University of Oregon researchers. Medical researchers have long known that cisplatin, a platinum compound used to fight tumors in nearly 70 percent of all human cancers, attaches to DNA. Its attachment to RNA had been assumed to be a fleeting thing, says UO chemist Victoria J. DeRose, who decided to take a closer look due to recent discoveries of critical RNA-based cell processes. "We're looking at RNA as a new drug target," she said.
"We think this is an important discovery because we know that RNA is very different in tumors than it is in regular healthy cells. We thought that the platinum would bind to RNA, but that the RNA would just degrade and the platinum would be shunted out of the cell. DeRose is now pursuing the ramifications of the findings. TACC supercomputers help researchers find deeper insight into structure and behavior of protein, DNA and RNA.
In 1926, Theodor Svedberg won the Nobel Prize in Chemistry for a novel method of separating proteins based on experiments performed on a new device he invented: the analytic ultracentrifuge. Analytical ultracentrifugation (AUC) experiments spin samples at very high speeds to study how large molecules such as proteins, DNA and RNA, act in solution. Under the influence of centrifugal forces up to 250,000 times as strong as Earth's gravity, materials undergo sedimentation and diffusion processes over time, revealing aspects of the individual molecules' natures. These processes are essential measurements for biochemists: a way to understand how molecules behave under physiological solution conditions. And 85 years later, scientists are still finding ways to make the analytic ultracentrifuge more useful.
AUC is also a very versatile tool to study composition. In 2004, Demeler and his colleague, Emre Brookes, began parallelizing the code so it could run on large-scale computer clusters. New research links common RNA modification to obesity. An international research team has discovered that a pervasive human RNA modification provides the physiological underpinning of the genetic regulatory process that contributes to obesity and type II diabetes. European researchers showed in 2007 that the FTO gene was the major gene associated with obesity and type II diabetes, but the details of its physiological and cellular functioning remained unknown. Now, a team led by University of Chicago chemistry professor Chuan He has demonstrated experimentally the importance of a reversible RNA modification process mediated by the FTO protein upon biological regulation. He and 10 co-authors from Chicago, China and England published the details of their finding in the Oct. 16 advance online edition of Nature Chemical Biology.
Scientists already had demonstrated that FTO removes methyl groups from nucleic acids, but only on one rare type of DNA or RNA methylation. Important but mysterious "RNA epigenetics? " Researchers find extensive RNA editing in human transcriptome. In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demonstrating the need for new robust methods to identify important post-transcriptional editing events.
RNA editing is a normal but not yet fully understood process in which small nucleotide changes occur after DNA has been transcribed into RNA. It is an integral step in generating diversity and plasticity of cellular RNA signature as a post-transciptional event that recodes hereditary information. RNA editing is an important area in the post-genomic era for its role in determining protein structure and function.
It has become increasingly important in genetic research. Last year, a study published in Science (Li, et al. Science, May 19, 2011) reported a large number of sequence differences between mRNA and DNA in the human transcriptome. PhysOrg Science News: Researchers find extensive... Researchers find extensive RNA editing in human transcriptome. Science Index: A nov... ResearchBlogging.org: Large intergenic noncoding... Plant biology: Plant Cell 'A new tool for... BioPortfolio Cancer: BioPortfolio News Enzo Bio... BioPortfolio Cancer: BioPortfolio News Enzo Bio...
MicroRNA molecule increases number of blood stem cells, may help improve cancer treatment. Investigators have identified a new mechanism that controls the number of hematopoietic stem cells - cells that give rise to all blood and immune system cells. In a report in the online Early Edition of Proceedings of the National Academy of Sciences, researchers from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute identify a tiny RNA molecule that increases the number of these blood stem cells, an advance that may improve treatment of blood system cancers.
"This novel molecule raises blood stem cell numbers by suppressing the normal cell-death process," explains David Scadden, MD, director of the MGH Center for Regenerative Medicine and senior author of the report. "We've known that these non-coding RNAs can define what an immature cell will become, but none has previously been identified that can tell a blood system stem cell whether to live or die.
" Human cells can copy not only DNA, but also RNA. Single-molecule sequencing technology has detected and quantified novel small RNAs in human cells that represent entirely new classes of the gene-translating molecules, confirming a long-held but unproven hypothesis that mammalian cells are capable of synthesizing RNA by copying RNA molecules directly. The findings were reported in Nature by researchers from the University of Pittsburgh School of Medicine, Helicos Biosciences Corp., Integromics Inc., and the University of Geneva Medical School.
"For the first time, we have evidence to support the hypothesis that human cells have the widespread ability to copy RNA as well as DNA," said co-author Bino John, Ph.D., assistant professor, Department of Computational and Systems Biology, Pitt School of Medicine. "These findings emphasize the complexity of human RNA populations and suggest the important role for single-molecule sequencing for accurate and comprehensive genetic profiling. " Micro-RNA determines malignancy of lung cancer. A small RNA molecule determines whether or not lung cancer cells grow invasively and metastasize. This has been discovered in the culture dish by scientists of the German Cancer Research Center and the University Medical Center Mannheim. Moreover, they found out that the following is true also for patients with non-small cell lung cancer: The less micro-RNA is produced by tumor cells, the higher the tumor's tendency to metastasize. Cancer becomes life-threatening when tumor cells start leaving their primary site.
They travel through the lymph and blood streams to other tissues where they grow into metastases. Professor Dr. "We believe that micro-RNAs also play an important role in metastasis and that they program cells in a way that leads to malignant growth," medical researcher Heike Allgayer explains. A dreaded characteristic of non-small cell lung cancer is its resistance to chemotherapy and targeted anticancer drugs. Now coming to your iPhone: App that shows 2-D structure of thousands of RNA molecules. (PhysOrg.com) -- For the first time, it's possible to experimentally capture a global snapshot of the conformation of thousands of RNA molecules in a cell.
The finding is important because this scrappy little sister of DNA has recently been shown to be much more complex than previously thought. "There's an app for that. " To a cadre of scientists, the familiar phrase will soon mean they can enter a specific RNA from baker's yeast into their iPhone and see a depiction of its two-dimensional structure - thanks to a new technology developed by scientists at Stanford University. The application is cool, but it's just window dressing for the real advance: For the first time, it's possible to experimentally capture a global snapshot of the conformation of thousands of RNA molecules in a cell.
The finding is important because this scrappy little sister of DNA has recently been shown to be much more complex than previously thought. Some of the patterns they identified were surprising. Nature study shows how molecules escape from the nucleus. By constructing a microscope apparatus that achieves resolution never before possible in living cells, researchers at Albert Einstein College of Medicine of Yeshiva University have illuminated the molecular interactions that occur during one of the most important "trips" in all of biology: the journey of individual messenger Ribonucleic acid (RNA) molecules from the nucleus into the cytoplasm (the area between the nucleus and cell membrane) so that proteins can be made.
The results, published in the September 15 online edition of Nature, mark a major advance in the use of microscopes for scientific investigation (microscopy). The findings could lead to treatments for disorders such as myotonic dystrophy in which messenger RNA gets stuck inside the nucleus of cells. Robert Singer, Ph.D., professor and co-chair of anatomy and structural biology, professor of cell biology and neuroscience and co-director of the Gruss-Lipper Biophotonics Center at Einstein, is the study's senior author. A mystery solved: How genes are selectively silenced. Cells read only those genes which are needed at a given moment, while the others are chemically labeled and, thus, selectively turned off.
Scientists at the German Cancer Research Center have now been the first to discover how these labels are placed at exactly the right spot in the genetic material. Important players are regulatory RNA molecules. They form a plait-like triple helix with the DNA serving as a signpost for the labels. Our genetic material is often compared to a book. However, it is not so much like a novel to be read in one piece, but rather like a cookbook. The cell reads only those recipes which are to be cooked at the moment. The recipes are the genes; 'reading' in the book of the cell means creating RNA copies of individual genes, which will then be translated into proteins. The cell uses highly complex, sophisticated regulatory mechanisms to make sure that not all genes are read at the same time. Grummt has now come much closer towards unraveling this mystery.
Identifying molecular guardian of cell's RNA. When most genes are transcribed, the nascent RNAs they produce are not quite ready to be translated into proteins - they have to be processed first. One of those processes is called splicing, a mechanism by which non-coding gene sequences are removed and the remaining protein-coding sequences are joined together to form a final, mature messenger RNA (mRNA), which contains the recipe for making a protein. For years, researchers have understood the roles played by the molecular machines that carry out the splicing process. But, as it turns out, one of those familiar components plays a new, and altogether unexpected role.
The researchers revealed an unexpected function for U1 in protecting mRNA transcripts from premature termination in addition to and independent of its role in splicing. As Dreyfuss puts it, "U1 is a guardian of the transcriptome. " SMN deficiency affects all snRNPs to one degree or another. Explore further: Japan stem cell scientist stands by 'phoney' research (Update) Evolutionarily young protein helps ancient RNA get into shape. The code for survival: Cells fight stress by reprogramming a system of RNA modifications.
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