Regulation of Alternative Splicing in Drosophila by 56 RNA Binding Proteins PDF Download
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Author:
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ISBN:
Category :
Languages : en
Pages : 10
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Book Description
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.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 10
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Book Description
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.
Author: Jefferson Matthew Taliaferro
Publisher:
ISBN:
Category :
Languages : en
Pages : 167
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Book Description
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.
Author: Rebecca Moschall
Publisher:
ISBN:
Category : Drosophila
Languages : en
Pages :
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Author: Jenny Marie Kreahling
Publisher:
ISBN:
Category :
Languages : en
Pages : 450
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Author: B. D. Hames
Publisher: Oxford University Press, USA
ISBN:
Category : Music
Languages : en
Pages : 238
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Book Description
This book gives a co-ordinated review of our present knowledge of eukaryotic RNA synthesis.
Author: Peter Gunning
Publisher: Springer Science & Business Media
ISBN: 0387857664
Category : Medical
Languages : en
Pages : 323
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Book Description
A recent review of one of my grant applications commented on the ‘rediscovery of tropomyosin’. I was tempted to write back in my rebuttal to the reviewer that I didn’t realise it had been lost. Uncharacteristic maturity prevailed and I resisted the temptation, but I was struck by the underlying observation that research on the str- ture and function of tropomyosin has been somewhat invisible, particularly in terms of the cytoskeleton isoforms. So, how can it be that one of the two major components of the actin filament has been so thoroughly overlooked? I suspect that the answer is disappointingly pedestrian. Whereas the biochemistry of the 1980s revealed the potential of tropomyosin isoforms to diversify the function of actin filaments, the subsequent disenchantment with isoform biology in general in the 1990s inhibited growth of this field. With the development of more sophisticated experimental - proaches we are now seeing a growing realisation of the importance of tropomyosin in regulating actin filaments beyond its pivotal role in muscle contraction. The opportunity to edit this book came at a time when we had written several reviews on different aspects of tropomyosin function and I had just finished the background reading for a comprehensive review of tropomyosin biology. I realised that the field was simply beyond the capacity of any one person to do the field j- tice.
Author: Philippe Jeanteur
Publisher: Springer Science & Business Media
ISBN: 3540344497
Category : Science
Languages : en
Pages : 265
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Book Description
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.
Author: Kiyoshi Nagai
Publisher: Oxford University Press, USA
ISBN:
Category : Medical
Languages : en
Pages : 302
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Book Description
The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.
Author: Adrian Krainer
Publisher: IRL Press
ISBN:
Category : Language Arts & Disciplines
Languages : en
Pages : 408
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Book Description
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.
Author: Philippe Jeanteur
Publisher:
ISBN: 9783662097298
Category :
Languages : en
Pages : 266
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Book Description
