Encyclopedia of Molecular Cell Biology and Molecular Medicine
Copyright © 1999-2012 by John Wiley and Sons, Inc. All Rights Reserved.
Online ISBN: 9783527600908
Editor(s): Dr. Robert A. Meyers
By Ashley Neff, Carol Wilusz and Jeffrey Wilusz
As part of our latest update on RNA Regulation, Jeffrey Willusz' team at Colorado State University have provided a detailed overview on mRNA stability and the processes, enzymes and regaultory factors that influence this in eukaryotic cells.
In eukaryotes, regulated mRNA stability plays a major role in determining the levels of gene expression. around 2--50% of changes in cellular gene expression can be attributed to alterations in mRNA stability, rather than transcription rates. RNA stability also plays a major role in determining the quality of overall gene expression within the cell.
Read more about how understanding mRNA decay processes is vital to the study and application of molecular cell biology here.
Although personalized medicine has a long history, today it implies low-variability responses to appropriately prescribed drugs. Achieving large reductions in variability of the responses to prescribed drugs requires reductions to be made in each of the many sources of variance: (i) the kinetics of drug release from formulated drug; (ii) the patients' variable adherence to prescribed dosing regimens; (iii) pharmacokinetics; and (iv) pharmacodynamics. To achieve a substantial reduction in overall variability requires substantial reductions in each principal source of variance. Pharmacogenomics underlies the biochemical mechanisms involved in both pharmacokinetics and pharmacodynamics, and advances in this area will most likely lead to reductions in variance arising from these two sources. This alone will not achieve the goal of making major reductions in the variability of responses to drug treatment, however. Rather, to achieve that goal – seen as the capstone of personalized medicine – will require comparable reductions to be made in all four major sources of variance in drug response.
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Personalized Medicine, by Alette Wessels, Robert Bies and John Urquhart is available here online and also in the new printed volume: Systems Biology.
Monozygotic Twins and Epigenetics
Twins have been the subject of both art and scientific investigation for millennia, more recently becoming crucial for exploring epigenetics – the potentially reversible DNA and chromatin modifications (e.g., methylation and acetylation) that regulate gene expression and other genomic functions. Monozygotic twins have near-identical DNA sequences, and offer unique opportunities to study epigenetic effects on phenotype, and the way in which epigenetic information is modified and maintained. The epigenetic code may also be transmitted across generations although, unlike the DNA code, epigenetic modifications may be modified by environmental inputs. Consequently, monozygotic twins become even more important for investigating the dynamic regulation and function of the epigenetic code.
Monozygotic Twins and Epigenetics by Jean-Sébastien Doucet and Albert H. C. Wong was published in the May 2012 update of the EMCBMM.
Previous spotlight articles:
Although the field of epigenetic medicine is relatively new, it continues to make great advances, due to and increased understanding of imprinted genes and the origins of epigenetic markings, the environmental effects on the epigenome and how these elements relate to both health and disease.
An understanding of the edpigenome, combined with knowledge of its origins and plasticity, has led to the creation of new methods for diagnosis and treatment. These include histone deacetylase inhibitors and methlation inhibitors that are capable of specifically targeting dysregulated genes, and consequently affecting abnormal cells more effectively than by applying "traditional" therapies.Epigenetic Medicine, by Randy Jirtle, Autumn Bernal and David Skaar
Understanding the regulation of the cell cycle, apoptosis, cell differentiation, cell signaling, cell signal transduction, and cell movement, to mention a few such phenomena; understanding the integration of their underlying molecular and cellular mechanisms; and understanding the developmental consequences of their operation, makes the early twenty-first century an exciting time to be a developmental cell biologist. It is also a hopeful time for those people suffering the ravages of dreadful diseases, such as cancer, and for those people awaiting the promise of regenerative medicine.
Synthetic Biology, by Sanjay Vashee, Mikkel A. Algire, Michael G. Montague and Michele S. Garfinkel, J. Craig Venter Institute, Synthetic Biology, Rockville, MD, USA.
The Human Epigenome, by Romulo Martin Brena
Epigenetic mechanisms are responsible for the transmission of information that is “layered onto” the DNA from one cell division to the next. That is, epigenetic information is not contained in the DNA sequence itself, but it is nonetheless essential for normal development, for maintaining the overall integrity of the genome, and for modulating gene dosage via processes such as imprinting and X-chromosome inactivation in females. Epigenetic modifications are reversible, which makes them an attractive therapeutic target for cancer and other diseases. DNA methylation is affected by nutrition and by environmental stimuli, which lends the epigenome a remarkable level of plasticity. DNA methylation is profoundly disrupted in cancer, and several techniques have been developed to analyze the cancer epigenome both globally and at the single gene level. Importantly, DNA methylation has been shown to serve as a biomarker. A large body of research is currently under way in the hope of identifying sequences that could lead to clinical applications. It should also be noted that DNA methylation inhibitors have been used in the successful treatment of myelodysplastic syndrome in human patients. This opens a promising avenue for the clinical treatment of solid tumors in the future.