Science Magazine: Sign In. Science Magazine: Sign In. Scripps research scientists devise screening method to aid RNA drug development research. Scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed a new method of screening more than three million combinations of interactions between RNA and small molecules to identify the best targets on RNA as well as the most promising potential drug compounds. This novel technology may lead to more efficient drug development. The study was published in the October 9, 2012 issue of the journal Nature Communications. RNA has multiple biological functions, including encoding and translating proteins from genes and regulating the amount of protein expressed under various cellular conditions.
Recent studies have identified RNA as a "molecular switch" that controls cellular events such as gene expression, making RNA an attractive target for small molecules that serve as chemical genetics probes, analytical tools or potential drugs. Source: Scripps Research Institute. Smallest and fastest-known RNA switches provide new drug targets. A University of Michigan biophysical chemist and his colleagues have discovered the smallest and fastest-known molecular switches made of RNA, the chemical cousin of DNA. The researchers say these rare, fleeting structures are prime targets for the development of new antiviral and antibiotic drugs.
Once believed to merely store and relay genetic information, RNA is now known to be a cellular Swiss Army knife of sorts, performing a wide variety of tasks and morphing into myriad shapes. Over the past decade, researchers have determined that most of the DNA in our cells is used to make RNA molecules, that RNA plays a central role in regulating gene expression, and that these macromolecules act as switches that detect cellular signals and then change shape to send an appropriate response to other biomolecules in the cell. Al-Hashimi calls these short-lived structures, which were detected using a new imaging technique developed in his laboratory, micro-switches. Source: University of Michigan. Sciencemagazine: Two subsets of multiple sclerosis... Sciencemagazine: #Gene loops keep #RNA polymerase... New study shows promise in using RNA nanotechnology to treat cancers and viral infections. Related images(click to enlarge) UK HealthCare A new study by University of Kentucky researchers shows promise for developing ultrastable RNA nanoparticles that may help treat cancer and viral infections by regulating cell function and binding to cancers without harming surrounding tissue.
The study, published in Nano Today, was carried out in the laboratory of Peixuan Guo, the William S. Farish Endowed Chair in Nanobiotechnology at the UK Markey Cancer Center, in collaboration with Dr. The study uses RNA (ribonucleic acid) as a building block for the bottom-up fabrication of nanostructures.
The study demonstrated that regulation of cellular functions progressively increased with the increasing number of functional modules in the nanoparticle. "RNA nanotechnology is an emerging field, but the instability and degradation of RNA nanoparticles have made many scientists flinch away from the research in RNA nanotechnology," Guo said. In addition to Evers and Markey team member Dr. Geologist calls for advances in restoration sedimentology.
Related images(click to enlarge) Indiana University Rapid advances in the new and developing field of restoration sedimentology will be needed to protect the world's river deltas from an array of threats, Indiana University Bloomington geologist Douglas A. Edmonds writes in the journal Nature Geoscience. The commentary, published this week in the November issue, addresses the fact that land is disappearing from river deltas at alarming rates. "There's a lot of talk about ecological restoration of the coast," Edmonds said. Under naturally occurring processes, coastal land is both created and destroyed at river deltas. But sea-level rise and coastal subsidence have tilted the scales toward land loss, and dams and levees built for flood control have interfered with the delivery of sediment. Edmonds says there is potential for restoring deltas by designing river diversions that direct sediment from rivers to areas where it can do the most good.
Edmonds holds the Robert R. Ancient enzymes function like nanopistons to unwind RNA. Molecular biologists at The University of Texas at Austin have solved one of the mysteries of how double-stranded RNA is remodeled inside cells in both their normal and disease states. The discovery may have implications for treating cancer and viruses in humans. The research, which was published this week in Nature, found that DEAD-box proteins, which are ancient enzymes found in all forms of life, function as recycling "nanopistons. " They use chemical energy to clamp down and pry open RNA strands, thereby enabling the formation of new structures. "If you want to couple fuel energy to mechanical work to drive strand separation, this is a very versatile mechanism," said co-author Alan Lambowitz, the Nancy Lee and Perry R.
In all cellular organisms RNA (ribonucleic acid) plays a fundamental role in the translation of genetic information into the synthesis of proteins. "Once the second domain is latched on to the RNA," said Mallam, "and the first has got its ATP, the 'piston' comes down. Science Magazine: Sign In. A programmable dual-RNA-guided DNA endonuclease in a... [Science. 2012. To cap or not to cap: Scientists find new RNA phenomenon that challenges dogma.
Some RNA molecules spend time in a restful state akin to hibernation rather than automatically carrying out their established job of delivering protein-building instructions in cells, new research suggests. And instead of being a fluke or a mistake, the research suggests that this restful period appears to be a programmed step for RNA produced by certain types of genes, including some that control cell division and decide where proteins will work in a cell to sustain the cell's life.
This could mean that protein production in cells is not as clear-cut as biology textbooks suggest, scientists say. Schoenberg and colleagues discovered this phenomenon by tracing the origins of a cap-like structure on messenger RNA (mRNA) that is known to coordinate most of this RNA molecule's short life.
Messenger RNA is manufactured in a cell's nucleus and each mRNA contains the instructions needed to produce a specific protein that a cell needs to live. "It wasn't random. Source: Ohio State University. E! Science News | Latest science news articles. Sciencemagazine: RNA-directed targeting system... Science Magazine: Sign In. Science Magazine: Sign In. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids.
We show here that in a subset of these systems, the mature crRNA that is base-paired to More Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA.
Science Magazine: Sign In. Sciencemagazine: RNA polymerase "clamp" opens... Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation. We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation More Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation.
We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation complex and remains closed during initial transcription and transcription elongation. We show that four RNAP inhibitors interfere with clamp opening. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules.
These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non–AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus More Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non–AUG-initiated, reading frames by distinct translational mechanisms.
Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. Science Magazine: Sign In. In different phases of the transcription cycle, RNA polymerase (Pol) II recruits various factors via its C-terminal domain (CTD), which consists of conserved heptapeptide repeats with the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7.
We show that the CTD of transcribing yeast Pol II is phosphorylated at Tyr1, in addition to Ser2, Thr4, Ser5, and More In different phases of the transcription cycle, RNA polymerase (Pol) II recruits various factors via its C-terminal domain (CTD), which consists of conserved heptapeptide repeats with the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. We show that the CTD of transcribing yeast Pol II is phosphorylated at Tyr1, in addition to Ser2, Thr4, Ser5, and Ser7. Tyr1 phosphorylation stimulates binding of elongation factor Spt6 and impairs recruitment of termination factors Nrd1, Pcf11, and Rtt103. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Science Magazine: Sign In. Sciencemagazine : The function, targets, and... Function, Targets, and Evolution of Caenorhabditis elegans piRNAs. Science Magazine: Sign In. Researchers achieve RNA interference, in a lighter package. Using a technique known as "nucleic acid origami," chemical engineers have built tiny particles made out of DNA and RNA that can deliver snippets of RNA directly to tumors, turning off genes expressed in cancer cells.
To achieve this type of gene shutdown, known as RNA interference, many researchers have tried -- with some success -- to deliver RNA with particles made from polymers or lipids. However, those materials can pose safety risks and are difficult to target, says Daniel Anderson, an associate professor of health sciences and technology and chemical engineering, and a member of the David H. Koch Institute for Integrative Cancer Research at MIT. The new particles, developed by researchers at MIT, Alnylam Pharmaceuticals and Harvard Medical School, appear to overcome those challenges, Anderson says. Because the particles are made of DNA and RNA, they are biodegradable and pose no threat to the body.
Genetic disruption Circulate and accumulate. Sciencemagazine: Inside Argonaute2, core pr... CSHL study uncovers a new exception to a decades-old rule about RNA splicing. There are always exceptions to a rule, even one that has prevailed for more than three decades, as demonstrated by a Cold Spring Harbor Laboratory (CSHL) study on RNA splicing, a cellular editing process. The rule-flaunting exception uncovered by the study concerns the way in which a newly produced RNA molecule is cut and pasted at precise locations called splice sites before being translated into protein. "The discovery of this exception could impact current ideas on how missteps in splicing triggered by mutations in the DNA sequence can lead to diseases such as cancer and various genetic disorders," says CSHL Professor Adrian Krainer, Ph.D., who led the research.
The study appears in the May 15 issue of Genes & Development. For a protein to be synthesized by the cell, the instructions encoded within that protein's gene have to be first copied from DNA into RNA. Krainer and Roca have now found a second, and much more prevalent, alternative option. Source: Cold Spring Harbor Laboratory. Researchers reveal an RNA modification influences thousands of genes. Over the past decade, research in the field of epigenetics has revealed that chemically modified bases are abundant components of the human genome and has forced us to abandon the notion we've had since high school genetics that DNA consists of only four bases.
Now, researchers at Weill Cornell Medical College have made a discovery that once again forces us to rewrite our textbooks. This time, however, the findings pertain to RNA, which like DNA carries information about our genes and how they are expressed. The researchers have identified a novel base modification in RNA which they say will revolutionize our understanding of gene expression.
Their report, published May 17 in the journal Cell, shows that messenger RNA (mRNA), long thought to be a simple blueprint for protein production, is often chemically modified by addition of a methyl group to one of its bases, adenine. The researchers uncovered links between m6A and other diseases as well. But Dr.
Sciencemagazine: High-res crystal structure... Science Magazine: Targeted delivery of siRNA... Strange cousins: Molecular alternatives to DNA, RNA offer new insight into life's origins. Related images(click to enlarge) The Biodesign Institute Arizona State University Living systems owe their existence to a pair of information-carrying molecules: DNA and RNA. These fundamental chemical forms possess two features essential for life: they display heredity -- meaning they can encode and pass on genetic information, and they can adapt over time, through processes of Darwinian evolution.
A long-debated question is whether heredity and evolution could be performed by molecules other than DNA and RNA. John Chaput, a researcher at ASU's Biodesign Institute, who recently published an article in Nature Chemistry describing the evolution of threose nucleic acids, joined a multidisciplinary team of scientists from England, Belgium and Denmark to extend these properties to other so-called xeno-nucleic acids or XNAs. The group demonstrates for the first time that six of these unnatural nucleic acid polymers are capable of sharing information with DNA.
Source: Arizona State University. Alexis verger: #siRNA #science A very com... A double ring ceremony prepares telomerase RNA to wed its protein partner. Related images(click to enlarge) Courtesy of Dr. Peter Baumann, Stowers Institute for Medical Research Few molecules are more interesting than DNA -- except of course RNA. After two decades of research, that "other macromolecule" is no longer considered a mere messenger between glamorous DNA and protein-synthesizing machines.
We now know that RNA has been leading a secret life, regulating gene expression and partnering with proteins to form catalytic ribonucleoprotein (RNP) complexes. One of those RNPs is telomerase, an enzyme that maintains chromosome integrity. In the March 25, 2012, advance online edition of Nature, researchers at the Stowers Institute for Medical Research report how the RNA TER1, a component of telomerase, is sculpted to favor interaction with its protein partner.
That processing is essential: without it TER1 could not engage its protein partner to form the active telomerase RNP. Ram Kannan of the Baumann lab also contributed to the paper. No comments please, we’ve made it through peer review (?) | Gene Expression. Twitter. Turning off small RNA. Turning off small RNA. Study of ribosome evolution challenges 'RNA World' hypothesis. MIT research: Delivering RNA with tiny sponge-like spheres. Computer sleuthing helps unravel RNA's role in cellular function. Scripps research scientists create novel RNA repair technology. Twitter. Sciencemagazine: Book "RNA: Life's Indispen... Twitter. CAD for RNA. Sciencemagazine: 2002 Breakthrough of the Y... Science Magazine: RNA processing factors reg... Cancer drug cisplatin found to bind like glue in cellular RNA. Sciencemagazine: Up close and personal with... Erasing the signs of aging in cells is now a reality.
Sciencemagazine: Follow the leader: how 5'-... Science Magazine: RNA Mimics of Green Fluore... Sciencemagazine: Hold and release: nucleoti... Science Magazine: Synthetic RNA nanostructur... Breakthrough lights way for RNA discoveries. Origin of life: enzyme-free copying of RNA. Study identifies mechanisms cells use to remove bits of RNA from DNA strands. Sciencemagazine: Defects in miRNA processin...
A molecular fossil of the RNA world. Hitting moving RNA drug targets. Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too. New research describes key function of enzyme involved in RNA processing. Researchers uncover a new level of genetic diversity in human RNA sequences. Science Magazine: Small, noncoding PIWI-inte... Webcasts. RNA dynamics deconstructed. Researchers construct RNA nanoparticles to safely deliver long-lasting therapy to cells. Science Magazine: HIV-1 RNA in genital mucos...
Science Magazine: Creation of an improved RN... Science Magazine: RNA splicing defects linke... UC San Diego chemists produce first high-resolution RNA 'nano square' Micro-RNA's contribute to risk for panic disorder.