Download or read book Regulation of Alternative Splicing written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2013-03-14 with total page 254 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 in Drosophila Melanogaster written by Jefferson Matthew Taliaferro and published by . This book was released on 2012 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: The patterns and mechanisms by which eukaryotic cells regulate the expression of their genetic information are highly complex and intricate. The transmittance of this information from nuclear repository to cytoplasmic translation contains within it several steps, including the selective removal and concomitant joining of pieces of information in a process called alternative splicing. The projects detailed within this document describe the regulation of alternative splicing through the interaction of specific proteins with specific pre-mRNA transcripts. The Rio lab has studied PSI, a protein involved in the regulation of the P element transposase transcript, for many years. It has since been shown to regulate the splicing of hundreds of other transcripts. The experiments described here look at the organization of PSI and other proteins on the P element transcript by site-specific labeling of the transcript using radioactive 32P. We also investigate two phosphorylation events of PSI, identifying the kinases responsible and demonstrate that these events may change the protein-protein interaction partners of PSI. It has become increasingly apparent that alternative splicing may not only be regulated by protein/RNA interactions, but also by RNA/RNA interactions. To probe this, we designed experiments to test if some well-known small RNA-associated proteins are regulating alternative splicing. Using splice junction microarrays, we determined that Argonaute-2 (Ago-2) regulated the splicing of over 100 splice junctions, and further experiments using ChIP-seq and mRNA-seq of Ago-2 mutants revealed that Ago-2 also has a role in transcriptional repression, possibly through being incorporating in complexes composed of polycomb-group genes. We also used CLIP-seq to determine the RNA binding profile and preferences of Ago-2 in Drosophila tissue culture cells. Finally, we characterized the functions of a Drosophila specific splicing factor called LS2. LS2 is orthologous to the highly conserved splicing factor dU2AF50, but its origin through retroduplication and subsequent divergence to acquire distinct sequence specificity, expression pattern, and function show it to be an interesting case in the evolution of alternative splicing regulation. This may be a mechanism that underlies the existence of some members of the large families of splicing factors, including hnRNP proteins and SR proteins. That is, by duplicating functional copies of genes, cellular systems create new proteins to tinker with and acquire new functions while keeping the former functionality and stability of the parent protein. While these projects are essentially independent of each other, they all fall under the umbrella of protein regulation of RNA metabolism and hopefully contribute to a more complete understanding of the regulation of gene expression.

Download or read book Regulation of Alternative Splicing in Drosophila written by Jenny Marie Kreahling and published by . This book was released on 2005 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Regulation of Alternative Pre MRNA Splicing of TAF1 in Drosophila Melanogaster written by Matthew S. Marengo and published by . This book was released on 2008 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Alternative Splicing in the Postgenomic Era written by Benjamin J. Blencowe and published by Springer Science & Business Media. This book was released on 2008-01-23 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: Yet again Springer has reached the market before everyone. This is the first book that is solely dedicated to the topic of alternative splicing. The book contains chapters by experts in the field that cover nearly all aspects of this hugely important subject. The purpose of the text is to provide a single, authoritative source of information on alternative splicing that is accessible to researchers in diverse fields. It is suitable for beginners and experts alike.

Download or read book RNA Splicing Regulation in Drosophila Melanogaster written by Angela Norie Brooks and published by . This book was released on 2011 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: A majority of metazoan genes contain introns in their primary transcripts (pre-mRNA) that require removal by the spliceosome--a cellular complex composed of protein and RNA. Upon removal of introns from the primary transcript, the remaining exonic portion of the transcript is spliced together. It is essential to remove the correct intronic portion of a primary transcript in order to produce the desired product, typically a protein-coding mRNA. Pre-mRNAs are alternatively spliced when different intron boundaries are used by the spliceosome, thus creating different mRNA products. Alternative splicing allows for an additional step of gene regulation by producing transcript isoforms that can be differentially processed in a particular tissue or developmental time point. Alternative splicing is primarily regulated by RNA binding proteins that bind to pre-mRNA and act to recruit or inhibit the spliceosome at specific splice sites. A central aim of this work is to gain a better understanding of splicing regulation by the identification and characterization of protein regulators of splicing and cis-acting splicing regulatory sequences in the model organism, Drosophila melanogaster. To identify splicing regulatory elements, many previous studies in vertebrate genomes have used computational methods. In collaboration with Anna I. Podgornaia, I applied such an approach to predict splicing regulatory elements in Drosophila melanogaster and compared them with elements found in vertebrates. I identified 330 putative splicing enhancer sequences enriched near weak 5' and 3' splice sites of constitutively spliced introns. I found that a significant proportion (58%) of D. melanogaster enhancers were previously reported as splicing enhancers in vertebrates. To provide additional evidence for the function of the intronic splicing enhancers (ISEs), I identified intronic hexamers significantly enriched within sequences phylogenetically conserved among 15 insect species. This analysis uncovered 73 putative ISEs that are also enriched in conserved regions of the D. melanogaster genome. The functions of nine enhancer sequences were verified in a heterologous splicing reporter by Julie L. Aspden, demonstrating that these sequences are sufficient to enhance splicing in vivo. Taken together, these data identify a set of predicted positive-acting splicing regulatory motifs in the Drosophila genome and highlight those regulatory sequences that are present in distant metazoan genomes. To identify and characterize splicing regulators, collaborators and I have combined RNAi and RNA-Seq to identify exons that are regulated by 58 known or putative splicing regulators. To identify and quantify alternative splicing events from RNA-Seq data, I developed the JuncBASE (Junction Based Analysis of Splicing Events) software package. For a pilot study, I identified 404 splicing events significantly affected upon depletion of pasilla. Preliminary analysis showed 879 splicing events affected by at least one of the 57 other proteins. The sequence regions upstream and within Pasilla-repressed exons and downstream of Pasilla-activated exons are enriched for YCAY repeats, which is consistent with the location of these motifs near regulated exons of the mammalian ortholog, Nova. Thus, the RNA regulatory map of Pasilla and Nova is highly conserved between insects and mammals despite the fact that the pre-mRNAs that are regulated by Pasilla and Nova are almost entirely non-overlapping. This observation strongly suggests that the regulatory codes of individual RNA binding proteins are nearly immutable, yet the regulatory modules controlled by these proteins are highly evolvable. I also present RNA regulatory maps for the four hnRNP proteins: hrp36, hrp38, hrp40, and hrp48. Lastly, I examine splicing regulation throughout the life cycle of D. melanogaster. Using transcriptome data from 30 developmental time points produced by collaborators from the modENCODE Consortium, I identified a total of 23,859 alternative splicing events in Drosophila, taking into account all transcript information from D. melanogaster annotations, short sequenced reads (Illumina RNA-Seq), sequenced cDNA, long RNA-Seq reads (454 RNA-Seq) from adult flies, and short read sequences of rRNA-depleted RNA from embryonic time points. I observed that 60.7% of intron-containing genes in D. melanogaster are alternatively spliced. Using only the Illumina RNA-Seq reads throughout development, 21,216 splicing events were expressed and 13,951 events were differentially spliced in at least one time point. I also observed exons with similar patterns of splicing changes throughout development as well as sex-biased alternative splicing. Integrating information from our pasilla study, I also observed correlations of pasilla gene expression with alternative splicing changes of its target exons throughout development.

Download or read book Regulation of Alternative Splicing in Drosophila by 56 RNA Binding Proteins written by and published by . This book was released on 2015 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. In conclusion, this large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.

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 Regulation of Translation and Alternative Splicing by the Drosophila RNA binding Protein Sister of Sex lethal written by Rebecca Moschall and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Eukaryotic MRNA Processing written by Adrian Krainer and published by IRL Press. This book was released on 1997 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on the major aspects of post-transcriptional mRNA processing in the nucleus of eukaryotic cells. Each of the described mRNA reactions is required for proper gene expression and can also serve as a control point for regulating the expression of many genes, for example duringembryonic development or in different cell types. The different chapters review the assembly of newly synthesized nuclear mRNA transcripts into hnRNP particles and catalytically active spliceosomes; the structure and mechanism of action of small nuclear ribonucleoprotein particles and proteinfactors that catalyse pre-mRNA splicing in mammalian cells and in yeast; the regulation of gene expression and generation of protein isoform diversity by alternative splicing; the mechanisms of 3' end cleavage and polyadenylation; the architecture of the cell nucleus in relation to these processesand to the localization of the relevant substrates and factors; the diverse mechanisms of RNA processing by ribozymes and their potential relevance for nuclear mRNA processing; the mechanism of spliced-leader addition by trans-splicing in nematodes and trypanosomes; and the process ofinsertion/deletion mRNA editing in kinetoplasmid protozoa. In each chapter, leading researchers have provided detailed, critical reviews of the history, experimental approaches, major advances, current ideas and models, as well as future directions, for each of these active areas of research.

Download or read book In Vivo Analysis of Alternative Pre mRNA Splicing written by David M. Standiford and published by . This book was released on 1996 with total page 36 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alternative splicing of pre-mRNA transcripts is normally an important mechanism to regulate the expression of many different protein isoforms including transcription factors and other regulatory proteins. Mis-regulation of alternative splicing can lead to the expression of inappropriate forms of such proteins in cells and has been shown to play a role in the establishing the cancerous state, enhancing the virulence of certain cancers, or inhibiting the treatments of cancer. The mechanisms that regulate alternative splicing have been investigated in Drosophila using the alternatively spliced myosin heavy chain gene as a model. The unique molecular and genetic tools provided by this system, have allowed the characterization of the elements that participate in permitting alternative splicing in general and have generated a model to explain the overall regulation of alternative splicing in this gene. The findings here are likely applicable to the understanding of other complex alternatively spliced genes.

Download or read book An Experimental and Genomic Approach to the Regulation of Alternative Pre mRNA Splicing in Drosophila Rnp 4f written by Rebecca A. Fetherson and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Rnp-4f, a Drosophila gene containing nine spliceosomal introns, encodes a nuclear PRP protein that functions constitutively in spliceosome assembly. Nothing is known about molecular mechanisms regulating splicing decisions for this gene, or the factors that modulate the degree of mRNA translation for the encoded spliceosomal assembly factor during development. Here we report results of a systematic study of alternative pre-mRNA splicing in rnp-4f. Reverse transcription-polymerase chain reaction (RT-PCR) and hybridization analysis show that introns #I - IV and #VI - VIII are constitutively spliced, while five patterns of alternative splicing are observed in two other pre-mRNA regions. Intron V is infrequently spliced in all developmental stages, which results in generation of an in-frame stop codon and a predicted truncated protein lacking a nuclear localization signal, so that facultative splicing regulates the subcellular localization of the encoded protein. Intron 0 plus a portion of exon 2 (intron-0-alt) is alternatively spliced from the 5'-UTR, resulting in loss of an evolutionarily conserved stem-loop located in exon 2. Northern analysis of poly (A+) mRNAs reveals two differently sized rnp-4f mRNA isomers, one dominating during mid-embryo stages of CNS development. The size of one of these mRNAs corresponds to that predicted for the constitutively spliced rnp-4f transcript. The other mRNA corresponds to the predicted size of the alternatively spliced transcript in which intron 0 plus a portion of exon 2 is excised, a result confirmed by hybridization. Potential molecular mechanisms which could regulate the observed splicing patterns are discussed, specifically from the viewpoint of putative cis-regulatory elements within rnp-4f pre-mRNAs. The alternative mRNA isoforms observed within the 5'-UTR are predicted to affect regulatory processes, including translational efficiency. A model is proposed in which RNP-4F controls its own level of expression by feedback against evolutionarily conserved twin stem-loops located at the 3'-end of the intron-0-alt pre-mRNA tract.

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 Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Analysis of the Regulation of Alternative Splicing of Myosin Alkali Light Chain Transcipts in Drosophila Melanogaster written by Efthimios Makis Charalambous Skoulakis and published by . This book was released on 1990 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Alternative Splicing Regulation of Drosophila Down Syndrome Cell Adhesion Molecule Gene written by Pinar Ustaogla and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Alternative Splicing Regulation of Drosophila Down Syndrome Cell Adhesion Molecule Gene written by Pinar Ustaoglu and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: