CCDC66 is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential
RNA splicing resulting in various isoforms in the retina.
To understand the molecular basis of these observations, we analyzed global
RNA splicing in Sf3b1
K700E / + hematopoietic cells.
The two studies link the loss of the SMN1 gene to defects in
RNA splicing of a critical neuronal gene, which leads to motor circuit dysfunction.
The therapy is an 18 - letter string of DNA that corrects aberrant splicing by binding a unique sequence on SMN2 «s messenger RNA located just downstream of the crucial seventh exon, thereby obstructing components of
the RNA splicing machinery (see «Bring to one's antisenses»).
U1 Small Nuclear Ribonucleoprotein Complex and
RNA Splicing Alterations in Alzheimer's Disease.
These compounds also corrected SMN2
RNA splicing and increased SMN protein levels in cell cultures obtained from SMA patients, including stem cell - derived motor neurons.
Investigates how
RNA splicing contributes to breast and ovarian cancer progression, metastasis and drug - resistance.
Functional analysis of genes with recurrent exons (i.e., with association with PMI in more than two tissues) shows a noteworthy enrichment on RNA binding and
RNA splicing genes (Supplementary Fig. 18b, c).
Multiple transcripts arising from alternative initiation or polyadenylation sites, or alternative
RNA splicing at a single locus were not considered as multiple genes but as variants of a single transcription unit.
Single - Molecule Imaging of
RNA Splicing in Live Cells.
Dr. Phillip Sharp's research has centered on the molecular biology of gene expression relevant to cancer and the mechanisms of
RNA splicing.
His landmark achievement was the discovery of
RNA splicing in 1977, for which he shared the 1993 Nobel Prize in Physiology or Medicine with Dr. Richard Roberts, who did parallel work at Cold Spring Harbor Laboratory.
«Our strategy to treat SMA relies on a simple, powerful antisense method that boosts SMN protein levels by fixing a genetic
RNA splicing glitch.
Harvard researchers have found a link between
the RNA splicing process and aging, which could lead to new treatments in helping humans live longer and healthier lives (Credit: halfpoint / Depositphotos)
Our genes provide the blueprints for producing the required proteins, and one of the main parts of that process is
RNA splicing, where RNA molecules are cut and reconnected to allow for more varied proteins to be expressed.
Now, a Harvard team has discovered a link between aging and a core biological process known as
RNA splicing, which may be manipulated to not only increase our lifespan, but help us stay healthier for longer.
RNA splicing antisense technology allows researchers to influence the ultimate structure and function of proteins.
Proteins are synthesized from instructions coded in the DNA through a multi-step process that includes
RNA splicing.
March 13, 2007 — Cold Spring Harbor, New York —
RNA splicing antisense technology studied at Cold Spring Harbor Laboratory (CSHL) effectively corrected an mRNA splicing defect found in spinal muscular atrophy (SMA) patients, and is now ready to be tested in mouse models.
Harvard researchers have found a link between
the RNA splicing process and aging, which could lead to new treatments in helping humans live longer and healthier lives
«These are fascinating results, and suggest that variability in
RNA splicing might be one of the smoking guns of the aging process,» says Mair.
Site - directed mutagenesis and kinetic analysis of
RNA splicing were used to identify a base triple in the conserved core of both a cyanobacterial (Anabaena) and a eukaryotic (Tetrahymena) group I intron.
The researchers utilized a technique known as exon skipping, a form of
RNA splicing, to eliminate the portion of one of the IgE receptor gene's mRNA that is essential to making a protein which places the IgE receptor on the mast cell surface.
Thus, the team has demonstrated a novel, positive role for PKR activation and eIF2 - alpha phosphorylation in human globin
RNA splicing, in contrast to the long - standing negative role of this intracellular stress response in protein synthesis.
Although this line of research is far from contributing to changes in the clinic, the team now has a much better understanding of how
RNA splicing is controlled in the ear.
«
RNA splicing machinery offers new drug target.»
But how do alterations in
RNA splicing result in hearing loss?
«It is already known that Rbfox is important for controlling
RNA splicing but what is not understood is its contribution to neuronal maturation and which specific cellular phenotypes it controls,» says Dr. Zhang.
«By being able to distinguish benign from malignant aging based on distinctive
RNA splicing patterns, we can develop therapeutic strategies that selectively target leukemia stem cells while sparing normal hematopoietic stem cells,» she said.
«Our findings show that
RNA splicing is a unique therapeutic vulnerability for secondary AML,» said Jamieson.
The authors say it's the first study to show
RNA splicing modulators inhibit cancer stem cell activity.
If disrupted,
RNA splicing could enhance the capacity of cells to propagate cancer.»
Using sensitive genetic sequencing technology, the scientists identified unique
RNA splicing variants that distinguish normal, aging stem cells from abnormal, malignant ones.
Crews noted that
RNA splicing - targeted agents have been shown to have activity in a variety of solid tumors so the findings may be relevant to a variety of cancers, such as breast and drug - resistant melanoma.
Shinde and Klein are not yet sure whether GSK - 3's effect on
RNA splicing explains its role in mood disorders.
«Alzheimer's: Newly identified protein pathology impairs
RNA splicing.»
Also on the list were several «U1 snRNP» proteins, which are involved in
RNA splicing.
What makes these tangles distinct is that they sequester proteins involved in
RNA splicing, the process by which instructional messages from genes are cut and pasted together.
«We were very surprised to find alterations in proteins that are responsible for
RNA splicing in Alzheimer's, which could have major implications for the disease mechanism,» says Allan Levey, MD, PhD, chair of neurology at Emory University School of Medicine and director of the Emory ADRC.
A form of genetic variation, called differential
RNA splicing, may have a role in tumor aggressiveness and drug resistance in African American men with prostate cancer.
As a consequence of differential
RNA splicing, mRNAs containing different combinations of exons can be produced from the same gene.
Like Kornblihtt's lab, alternative
RNA splicing makes use of constrained resources in innovative ways.
In fact, he and his community of researchers in alternative
RNA splicing — a field he helped to create — have shown that they can do world - class research despite tight government budgets and three - month delivery times for reagents that can cost three times as much as they would in the United States or Europe.
Nor is RNA quite so inert or structurally constrained as its cousin; its conformational versatility and catalytic abilities have been implicated at the very core of protein synthesis and possibly of
RNA splicing.
Coupling of Tetrahymena ribosomal
RNA splicing to beta - galactosidase expression in Escherichia coli
The beta - galactosidase messenger
RNA splicing system provides a useful method for screening for splicing - defective mutations, several of which have been characterized.
Not exact matches
(Ligases are enzymes that
splice together other molecules such as DNA or
RNA.)
Thus
RNA self -
splicing can occur at a rate sufficient to support gene expression in a prokaryote, despite the likely presence of ribosomes on the nascent
RNA.
The chemical mechanisms of
RNA - catalyzed reactions are discussed with emphasis on the self -
splicing ribosomal
RNA precursor of Tetrahymena and the enzymatic activities of its intervening sequence
RNA.
Splicing in vitro of a messenger
RNA (mRNA) precursor (pre-mRNA) is inhibited by a monoclonal antibody to the C proteins (anti-C) of the heterogeneous nuclear
RNA (hnRNA)- ribonucleoprotein (hnRNP) particles.