Download or read book Alternative Splicing and Cancer written by Muzafar A. Macha and published by CRC Press. This book was released on 2024-05-03 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book Alternative Splicing and Cancer explores the crucial role alternative splicing, a post-transcriptional process, plays in human health and diseases, particularly cancer. Diving deep into the complexities of gene expression and protein diversity, the book illuminates how abnormal splicing contributes to aggressive tumor formation, affecting cellular functions such as proliferation, survival, and immune evasion. With a focus on understanding molecular mechanisms, this book unravels potential diagnostic and prognostic targets, opening doors for enhanced anti-cancer treatment efficacy. An indispensable resource for anyone intrigued by the interplay between gene splicing and cancer biology, it paves the way towards innovative therapeutic strategies.
Download or read book Alternative Splicing and Disease written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2006-10-04 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.
Download or read book Alternative Splicing in Brain Function written by Kif Liakath-Ali and published by Frontiers Media SA. This book was released on 2023-12-13 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Functional and structural intricacies of biological systems emerge from the complex nature of the genome. A key aspect of genome complexity can be attributed to the process of alternative splicing of precursor mRNA (or pre-mRNA), during which introns are removed and exons are selectively spliced together. This highly regulated process generates different mature mRNA transcripts from a single gene and is widespread throughout the eukaryotic evolution. The majority of the genes expressed in the mammalian central nervous system undergo extensive alternative splicing. Some genes can generate more than a thousand isoforms resulting in diverse proteoforms that can differ in their function, binding preference, catalytic activity, and localization. Perturbation in alternative splicing has been linked to many neurological disorders. Despite its significance, we still lack a comprehensive understanding of its role in neuronal function. Recent studies suggest that alternative splicing is a regulator of tissue identity and development. This is particularly relevant to the brain where developmental regulation and heterogenous cell population play a crucial role in shaping its function. For a long time, technological limitations in detecting and measuring alternatively spliced transcripts hindered the progress in understanding the biology of alternative splicing. Recent advances in long-read and native mRNA sequencing and robust computational tools allow us to capture and quantify in their full-length form. Public transcriptomics datasets can be utilized for the meta-analysis of alternative splicing landscapes of various experimental conditions and disease samples. In addition, protein isoform detection complements mRNA isoform levels. Given its biological significance and recent advances, the objective of this Research Topic is to assemble current knowledge, views, and challenges in the studies of alternative splicing in brain function.
Download or read book Bioinformatics in the Era of Post Genomics and Big Data written by Ibrokhim Y. Abdurakhmonov and published by BoD – Books on Demand. This book was released on 2018-06-20 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bioinformatics has evolved significantly in the era of post genomics and big data. Huge advancements were made toward storing, handling, mining, comparing, extracting, clustering and analysis as well as visualization of big macromolecular data using novel computational approaches, machine and deep learning methods, and web-based server tools. There are extensively ongoing world-wide efforts to build the resources for regional hosting, organized and structured access and improving the pre-existing bioinformatics tools to efficiently and meaningfully analyze day-to-day increasing big data. This book intends to provide the reader with updates and progress on genomic data analysis, data modeling and network-based system tools.
Download or read book Alternative Splicing in Cancer written by and published by . This book was released on 2006 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Elucidating Mechanisms of Alternative Splicing in Cancer and Cellular Stress written by Matias Ignacio Montes Serey and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative splicing of the pre-mRNA is an essential post-transcriptional process in eukaryotes that generates multiple protein isoforms from a single gene. However, this process can be disrupted by mutations leading to several diseases including cancer. One such example is the oncogene and negative regulator of p53 Mouse Double Minute 2 homolog (MDM2), which undergoes alternative splicing to produce a splice isoform that has novel implications in cancer development. MDM2-Alt1 comprised of coding exons 3 and 12, is highly expressed in several cancers including those of the breast, liposarcomas, high-grade gliomas and rhabdomyosarcomas (RMS), and can be induced by genotoxic stress. Another good example of cancer-related aberrant alternative splicing, is the insulin receptor gene (INSR), comprised of 22 exons, and that skipping of the exon 11 allows the production of the IR-A splice isoform. Overexpression of the IR-A isoform compared to the full-length IR-B isoform, has been reported in several cancers including RMS, osteosarcoma, breast cancer, prostate cancer and hepatocellular carcinoma. Understanding of the splicing mechanisms of these two genes is crucial to improve current cancer therapies. In this work we report that SRSF2 positively regulates the alternative splicing of MDM2 and that its binding to the exon 11 can be modulated to generate novel mouse model for cancer studies. Furthermore, we show a novel and unique regulatory mechanism of splicing wherein a nuclear microRNA, miR-29b, influences the alternative splicing of MDM2 by directly binding to the MDM2 pre-mRNA. We show that miR-29b is downregulated by genotoxic stress, a similar characteristic of cancer cells. Finally, we study the usage of antisense oligonucleotides (ASOs) as cancer therapies, by blocking the binding of the CUG-BP1 (CUG Binding Protein 1) splicing factor with an ASO, we promote the alternative splicing of the IR-B isoform which decreases cell proliferation and angiogenesis. Moreover, modulation of the MBNL1 (Muscleblind Like 1) intronic splicing enhancer in the intron 11 of the INSR, set the foundation for a novel mouse model to study this aberrant alternative splicing. Overall, our study underscores the importance of understanding alternative splicing in cancer research, moreover, it expands the knowledge regarding the complex splicing mechanisms involved in disease and finally set the foundations for the design of novel and effective splice-switching cancer therapies.
Download or read book Cancer Stem Cells written by Federica Papaccio and published by Springer Nature. This book was released on with total page 263 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Cell Transformation written by Johng S. Rhim and published by Springer Nature. This book was released on 2019-10-01 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, part contributed volume, part proceedings, discusses state-of-the-art advances on human cell transformation in cell models for the study of cancer and aging. Several of the chapters are from the Human Cell Transformation: Advances in Cell Models for the Study of Cancer and Aging conference that was held in June 2018 at McGill University. The authors represent international expertise on a wide variety of topics ranging from different types of cancer (prostate, bone, breast, etc.) to tumor microenvironment, tumor progression, homogeneity, and possible therapies and treatments.
Download or read book RNA Splicing and Backsplicing Disease and Therapy written by Rosanna Asselta and published by Frontiers Media SA. This book was released on 2020-12-24 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Download or read book Alzheimer s and Parkinson s Diseases written by Israel Hanin and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 690 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book represents the third in a series of International Conferences related to Alzheimer's (AD) and Parkinson's (PD) diseases. The first one took place in Eilat, Israel, in 1985; and the second one in Kyoto, Japan, in 1989. This book contains the full text of oral and poster presentations from the Third International Conference on Alzheimer's and Parkinson's Diseases: Recent Developments, held in Chicago, Illinois, U.S.A. on November 1-6, 1993. The Chicago Conference was attended by 270 participants. The Scientific Program was divided into nine oral sessions, a keynote presentation, and a poster session. The conference culminated in a Round Table Discussion involving all of the participants in the conference. The four and one-half day meeting served as an excellent medium for surveying the current status of clinical and preclinical developments in AD and PD. There were 59 oral presentations and 93 posters. This book incorporates a majority of both.
Download or read book The Role of Alternative Splicing in Breast Cancer Progression written by and published by . This book was released on 2007 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative pre-mRNA splicing generates thousands of different mRNA isoforms in metazoan organisms. It is unknown if breast-cancer associated alternative splicing is regulated like tissue-specific splicing, or whether it is caused by changes in the splicing accuracy. To test the hypothesis that the accuracy of the spliceosome is compromised in breast tumor cells, we have designed a quantitative real-time PCR assay to determine the number of incorrectly spliced mRNA products made from pre-mRNA transcripts that produce only a single mRNA product in all eukaryotic genomes. Analysis of all possible alternative exon exclusion patterns for these genes demonstrates that in some cases a splicing mistake is made only once in 25,000 intron removal events. These results demonstrate that the error rate of the spliceosome is extremely low. Using this assay we examined splicing error rates in breast cancer cell lines. Using matched cancer and normal cell lines we demonstrated that breast cancer cell lines exhibit an up to 3-fold decrease in the number of splicing errors. We conclude that perturbed pre-mRNA splicing in breast cancer is mediated in part through alterations of the intrinsic fidelity of the spliceosome.
Download or read book Deciphering the Molecular Mechanism of Alternative Splicing Changes in Cancer written by Taegyun Yang and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative splicing (AS) is an elaborately regulated molecular process incorporating different exons, expanding the proteome diversity from a single gene. AS is involved in virtually all biological processes and diseases, in which the AS process is often dysregulated. Dysregulated AS in cancer is so prevalent that it is now considered a hallmark of cancer. This dysregulation introduces a novel modality to target cancer through splicing modulation. Recent developments in RNA-Sequencing technologies have enabled transcriptome-wide quantification of AS changes in biological processes and diseases, requiring the development of computational methods for deciphering the molecular regulatory mechanisms for the observed AS changes in biological processes, diseases, and treatments.AS process is regulated by multitudes of RNA binding proteins (RBPs), each playing unique roles in the splicing processes, where molecular changes in RBPs causes AS changes in biological processes. Thus, the mechanism of AS changes can be attributed to molecular changes in RBPs, but determining the causal RBPs, based on the observed AS changes, has been challenging due to the complexity of AS regulation. We present Splicing Profile Analysis using RBP KD/KO Signatures (SPARKS), a computational framework to infer causal RBPs by quantifying the similarity in AS between the study of interest and the perturbation of RBPs from a large-scale RBP perturbation database. We verified that splicing factor perturbation leads to unique AS changes, which SPARKS leverages to identify causal RBPs. We demonstrated the efficacy of SPARKS in identifying the causal RBPs in RBP perturbation experiments and biological processes with known regulatory mechanisms in AS. We applied SPARKS to the AS changes in AML patients with the recurrent somatic mutation in U2AF1 and uncovered that the mutant U2AF1 and PTBP1 are involved in the AS changes. We also discovered the candidate RBPs responsible for pan-cancer AS changes upon PRMT5 inhibition therapy, EFTUD2, PCBP2, and PRPF8. Integrating the molecular changes on the candidate RBPs, we generated a potential model for the mechanism of action for PRMT5 inhibition in splicing. In summary, this work illustrates a computational analysis framework to decipher the molecular mechanisms of alternative splicing regulation in biology, disease, and therapy.
Download or read book Exploring Alternative Splicing in Cancer written by and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genomic characterization of cancer subtypes became a major research goal worldwide after the release of the complete human genome sequence in 2001. International consortia (e.g. The Cancer Genome Atlas - TCGA) have profiled and analyzed large numbers of human tumors matched to non-malignant tissues and created databases of molecular aberrations at the DNA, RNA, protein and epigenetic level. Research efforts aimed at understanding the molecular determinants of cancer prompted the rapid development of molecularly targeted chemotherapeutics which significantly improved clinical outcomes. Unfortunately, most cancer patients experience disease relapse manifested as recurrence of residual malignant cells which apparently did not respond to treatment regimes. Such cells either already carried or acquired genetic alterations (e.g. mutation, gene amplification, gene deletion or chromosomal translocation) that provide a clonal advantage to survive under selective therapeutic pressure. DNA aberrations have largely been documented to activate and drive oncogenic transformation as well as modulate response to therapy. Recent evidence highlighted the connection between alternative pre-mRNA splicing, cancer development and response to therapy. Alternative splicing is the essential process in eukaryotic gene expression by which non-coding intron sequences are removed from the pre-mRNA transcripts and specific exons are included or excluded from mature mRNAs. The aim of this thesis is to unravel the role of altered splicing in drug-resistant pediatric leukemia and evaluate the efficacy of small molecule splicing modulators in rare and aggressive tumors which pose major therapeutic challenges in the adult population. Chapter 2 is an extensive overview of the latest findings in the field of alternative splicing regulation in cancer.
Download or read book Regulation of Alternative Splicing written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2002-10-21 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery in 1977 that genes are split into exons and introns has done away with the one gene - one protein dogma. Indeed, the removal of introns from the primary RNA transcript is not necessarily straightforward since there may be optional pathways leading to different messenger RNAs and consequently to different proteins. Examples of such an alternative splicing mechanism cover all fields of biology. Moreover, there are plenty of occurrences where deviant splicing can have pathological effects. Despite the high number of specific cases of alternative splicing, it was not until recently that the generality and extent of this phenomenon was fully appreciated. A superficial reading of the preliminary sequence of the human genome published in 2001 led to the surprising, and even deceiving to many scientists, low number of genes (around 32,000) which contrasted with the much higher figure around 150,000 which was previously envisioned. Attempts to make a global assessment of the use of alternative splicing are recent and rely essentially on the comparison of genomic mRNA and EST sequences as reviewed by Thanaraj and Stamm in the first chapter of this volume. Most recent estimates suggest that 40-60% of human genes might be alternatively spliced, as opposed to about 22% for C. elegans.
Download or read book Regulation of Alternative Splicing and Its Connections to Cancer written by Mo Chen and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: I examined the mechanism of spliceosomal A complex formation and found that SRp38 promotes the recruitment of U1 and U2 snRNPs to splicing substrates that contain high-affinity SRp38 binding sites.
Download or read book Genome wide Analysis of Tissue specific and Cancer specific Alternative Splicing in the Human Transcriptome written by Qiang Xu and published by . This book was released on 2004 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Synthetic Biology written by Christina Smolke and published by John Wiley & Sons. This book was released on 2018-02-28 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: A review of the interdisciplinary field of synthetic biology, from genome design to spatial engineering. Written by an international panel of experts, Synthetic Biology draws from various areas of research in biology and engineering and explores the current applications to provide an authoritative overview of this burgeoning field. The text reviews the synthesis of DNA and genome engineering and offers a discussion of the parts and devices that control protein expression and activity. The authors include information on the devices that support spatial engineering, RNA switches and explore the early applications of synthetic biology in protein synthesis, generation of pathway libraries, and immunotherapy. Filled with the most recent research, compelling discussions, and unique perspectives, Synthetic Biology offers an important resource for understanding how this new branch of science can improve on applications for industry or biological research.
