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Book Identification and Characterization RNA Binding Proteins Involved in Post transcrptional Control of Caenorhabditis Elegans Germline Development

Download or read book Identification and Characterization RNA Binding Proteins Involved in Post transcrptional Control of Caenorhabditis Elegans Germline Development written by Brian C. Kraemer and published by . This book was released on 2000 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Characterization of RNA binding Proteins Involved in Post transcriptional Regulation

Download or read book Characterization of RNA binding Proteins Involved in Post transcriptional Regulation written by Gerrit Martin Daubner and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book RNA Binding Proteins

    Book Details:
  • Author : Zdravko Lorkovic
  • Publisher : CRC Press
  • Release : 2012-08-10
  • ISBN : 149871336X
  • Pages : 174 pages

Download or read book RNA Binding Proteins written by Zdravko Lorkovic and published by CRC Press. This book was released on 2012-08-10 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression in eukaryotes is regulated at different levels, which need to be coordinated to implement the information in the genome. Now it is clear that post-transcriptional regulation of gene expression such as pre-mRNA splicing, mRNA transport, editing, turnover and translation are as important as the control of transcription. In all aspects

Book Identification and Characterization of Three RNA Helicase A Binding Proteins and Their Roles in the Post transcriptional Regulation of Simple Retroviruses

Download or read book Identification and Characterization of Three RNA Helicase A Binding Proteins and Their Roles in the Post transcriptional Regulation of Simple Retroviruses written by Christopher Bryant Westberg and published by . This book was released on 2002 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book RNA binding Protein Mediated Post transcriptional Control of Gene Expression in Eye Development and Disease

Download or read book RNA binding Protein Mediated Post transcriptional Control of Gene Expression in Eye Development and Disease written by Soma Dash and published by . This book was released on 2018 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Eye development in vertebrates is initiated in late gastrulation and involves coordinated morphogenesis between the optic vesicle and the non-neural surface ectoderm resulting in the formation of the neural retina and the lens, respectively. While transcription and signaling events required for eye development are well understood, post-transcriptional control of gene expression, especially mediated by RNA-binding proteins (RBPs) is less clear. This represents a significant knowledge-gap as RBPs are important regulatory molecules in the cell that can control the fate of their target mRNAs by interacting with them throughout the mRNA life-cycle and mediating their processing, intra-cellular transport and localization, stability, translation into protein, and ultimately, their degradation. This is also a significant knowledge gap because there are similar number of RBPs encoded by the human genome as there are transcription factors, but the former class of proteins are not as well understood in the context of organogenesis and birth defects as compared to the latter. ☐ While high-throughput sequencing has identified several RBPs to be expressed in the eye, the functional significance in eye development for the vast majority of these factors is yet to be determined. Recently, the Lachke laboratory has identified two conserved RBPs required for eye development, Tdrd7 and Celf1, whose deficiency in the lens results in cataract in vertebrates. To further investigate the importance of RBP-mediated post-transcriptional gene expression control in eye development, I applied a systems-based bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery) to identify two new RBPs, Rbm24 and Caprin2, which are enriched during early mouse lens development, but whose molecular function in eye development had thus far not been determined. In this research dissertation, I have characterized the function of both Rbm24 and Caprin2 using constitutive and conditional targeted gene deletion mouse models. Further, in collaboration with Dr. Diane Slusarski’s laboratory (University of Iowa), zebrafish rbm24a knockout (by CRISPR/Cas9) and knockdown (by morpholino) mutants were generated and characterized. Together, these findings have led to a comprehensive understanding of the function of these RBPs in vertebrate eye development. ☐ Rbm24-targeted deletion in mouse and rbm24a-CRISPR/Cas9-targeted knockout or morpholino-knockdown in zebrafish causes the developmental defects microphthalmia (small eye) or anophthalmia (no eye). Rbm24 deficiency leads to apoptotic defects in the mouse ocular tissue as well as downregulation of eye development markers such as Sox2, Lhx2, Jag1, E-cadherin and g-Crystallins. Further, similar to the observations in the mouse, sox2 expression is also found to be reduced in rbm24a-morphant zebrafish, indicating the conservation of the Rbm24-Sox2 regulatory module in vertebrate eye development. About 20% of human anophthalmia cases are linked to SOX2 mutations alone. Therefore, I focused on investigating the post-transcriptional molecular mechanism of Rbm24-mediated Sox2 regulation. Sox2 is an intronless gene whose encoded mRNA contains AU-rich regions (ARE) in its 3’UTR. Interestingly, Rbm24 is known to bind to ARE sites in target mRNA. Therefore, to test if Rbm24 directly binds to Sox2 mRNA in vitro and in vivo, I performed RNA-Electrophoretic Mobility Shift assay (EMSA) and RNA-Immunoprecipitation (RIP), respectively. RNA-EMSA showed that Rbm24 protein directly binds to a 20 bp oligomer based on the mouse Sox2 mRNA sequence, and that an intact ARE is necessary for this protein-RNA binding. In turn, RIP assay on E14.5 wildtype mouse ocular tissue suggests that Rbm24 directly binds to Sox2 mRNA in vivo in eye development. To understand the biological significance of this direct Rbm24 protein-Sox2 mRNA molecular interaction, I performed an RNA-decay assay in NIH3T3 cells by co-transfected them with an Rbm24-overexpression vector and a Renilla luciferase reporter vector. In this assay, the Renilla luciferase gene ORF (open reading frame) is fused with the mouse Sox2 mRNA 3’UTR, which contains the three intact ARE sites, and reporter transcripts were quantified after Actinomycin-D treatment to transfected cells. This analysis demonstrates that in conditions of Rbm24 over-expression, the intact Sox2 3’UTR can render increased stability to the reporter transcript. Thus, Rbm24 positively controls Sox2 expression by binding to ARE sites in its 3’UTR and increasing its mRNA stability. Further, mutation analysis in the RNA-decay assay extends the in vitro observation that the binding of Rbm24 to the Sox2 mRNA 3’UTR depends on ARE by providing in vivo evidence that the presence of the ARE sites is necessary for the stability effect rendered by the Sox2 mRNA 3’UTR upon Rbm24 overexpression. Further, because Sox2 is one of the original four Yamanaka pluripotency/cellular reprogramming factor (along with Oct4, Klf4 and c-Myc), I investigated the impact of Rbm24 on the expression of other reprogramming factors such as Oct4, Klf4, c-Myc as well as, Nanog, another established pluripotency factor. I find that over-expression of Rbm24 in several different cell lines such as NIH3T3 (mouse embryo fibroblast cell line), 21EM15 (mouse lens epithelial cell line) and C2C12 (mouse myoblast cell line) results in the up-regulation of Sox2, Oct4 and Klf4. Further, in Rbm24-overexpressed C2C12 cells, Nanog and c-Myc are also upregulated. These data highlight that Rbm24 mediates post-transcriptional control of key transcription and pluripotency factors in vertebrate development. ☐ To gain insight into the function of the other newly identified RBP, Caprin2, in lens biology, I first performed expression analysis of Caprin2 in mouse lens development using in situ hybridization, western blotting and immunostaining. These experiments validate the iSyTE prediction that Caprin2 mRNA and protein are highly expressed and enriched in mouse embryonic and postnatal lens. I generated lens-specific Caprin2 conditional knockout (cKO) mouse mutants using a lens-Cre deleter line Pax6GFPCre. Phenotypic analysis of Caprin2cKO/cKO mice, wherein Caprin2 is expected to be deleted in the lens starting from E9.5 due to Cre-mediated re-arrangement of the Caprin2 alleles, revealed two distinct eye defects at variable penetrance. Wheat germ agglutinin staining and scanning electron microscopy demonstrated that Caprin2cKO/cKO mutants have an abnormally compact “lens nucleus”, which is the core of the lens comprised of centrally located terminally differentiated fiber cells. Further, at a reduced penetrance (8%), I find that Caprin2cKO/cKO mutants exhibit an ocular defect wherein the lens and the cornea remain attached by a persistent stalk, resembling the human developmental defect termed Peters anomaly. These data suggest that a conserved RBP Caprin2 functions in distinct morphological events in mammalian eye development. ☐ Together the findings in this dissertation have demonstrated that conserved RBPs such as Rbm24 and Caprin2 have evolved distinct functions in vertebrate eye development and their deficiency leads to microphthalmia and anophthalmia, and lens defects and Peters anomaly, respectively, thus impacting the study of ocular defects in humans.

Book Germline Stem Cells

    Book Details:
  • Author : Steven X. Hou
  • Publisher : Humana Press
  • Release : 2014-10-15
  • ISBN : 9781617378805
  • Pages : 0 pages

Download or read book Germline Stem Cells written by Steven X. Hou and published by Humana Press. This book was released on 2014-10-15 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this comprehensive and cutting-edge book, leading experts explore the parameters that define germline stem cells and the mechanisms that regulate the cell behavior in order to better isolate, characterize and maintain them. The volume begins by providing protocols for germline stem cell identification and regulation in model organisms, and concludes with detailed chapters covering current techniques involving in vitro culture and the applications of the cells.

Book Protein binding and RNA binding Properties of RNA binding Proteins FBF and RBM39

Download or read book Protein binding and RNA binding Properties of RNA binding Proteins FBF and RBM39 written by Joann Wu and published by . This book was released on 2012 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Post-transcriptional regulation of gene expression is critical in the development, physiology, and reproduction of multicellular organisms. Large dynamic multi-protein complexes formed through extensive protein*protein and protein*RNA interactions control mRNA processing, splicing, nuclear transport, localization, stability, and translation. However, despite the biological importance of these regulatory complexes, there is sparse molecular information describing the interactions involved in their assembly. In these studies, two categories of RNA-binding proteins that act as foundations for these complexes are examined: the Pu milio and F[barbelow]BF (PUF) proteins and R[barbelow]NA r[barbelow]ecognition m[barbelow]otif (RRM) domain-containing proteins. While there is a wealth of knowledge for PUF protein interactions with RNA, there is limited information describing the equally essential interactions between PUF proteins and their protein binding partners. Defined in these studies are the molecular bases for the developmentally essential interactions between Caenorhabditis elegans PUF protein f[barbelow]em-3 b[barbelow]inding f[barbelow]actor (FBF) and the two protein binding partners: g[barbelow]erml[barbelow]ine d[barbelow]evelopment defective-3[barbelow] (GLD-3) and c[barbelow]ytoplasmic p[barbelow]olyadenylation element b[barbelow]inding-1 (CPB-1). Short specific sequences in unstructured regions of the GLD-3 and CPB-1 proteins are critical for interaction with FBF, while a loop connecting PUF repeats R7 and R8 in FBF is essential for association with both GLD-3 and CPB-1. The PUF protein*binding partner complex FBF*GLD-3 is capable of forming a stable complex on RNA FBF regulatory elements in the 3' u[barbelow]nt[barbelow]ranslated r[barbelow]egions (UTR) of specific germline developmental mRNAs, and may control their expression through several proposed mechanisms. Although the RRM domains that characterize RRM-containing proteins adopt the same vary greatly in: amino acid sequence; DNA, RNA, and protein-binding abilities; and mode of interaction with these biological molecules. These studies potentially identify the first member of a unique class of RRMs that bind to RNA in a manner similar to RRMs that interact with proteins. These studies characterizing the protein- and RNA-binding properties of these RNA-binding proteins provide insight into the biologically essential molecular complexes involved in post-transcriptional gene regulation.

Book RNA protein Interactions

Download or read book RNA protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Book Post transcriptional Coordination by an RNA binding Protein

Download or read book Post transcriptional Coordination by an RNA binding Protein written by Joshua Jaeger Wolf and published by . This book was released on 2010 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA-binding proteins can regulate the stability, localization, and translation of their target mRNAs. Post-transcriptional regulation can orchestrate dynamic changes in gene expression, and can coordinate multiple cellular processes in response to various stimuli. Filamentous growth in Saccharomyces cerevisiae is a morphogenetic switch that occurs in response to nitrogen starvation and requires alterations in cell growth, cell cycle, and cell wall functions. Tyl element retrotransposition is also induced under conditions of nitrogen starvation. I describe a role for the RNA-binding protein Khdl in regulating these two responses to environmental stress through its mRNA targets. I identified the RNA targets of Khdl using in vivo crosslinking and immunoprecipitation (CLIP), combined with deep sequencing. This produced a high-resolution map of Khdl binding sites across the transcriptome, and provided unprecedented insight into its biological functions. Khdl regulates multiple post-transcriptional regulatory loops to coordinate the components of filamentous growth and Tyl retrotransposition. Although similar mechanisms were known to transcriptionally regulate these processes, the posttranscriptional coordination is a novel discovery. The feed-forward regulation that Khdl confers on FLO11, which encodes a protein required for filamentous growth, enables asymmetric expression between mother and daughter cells to switch between filamentous and yeast form growth. In this thesis, I describe regulation of gene expression by RNA-binding proteins, methods to identify their target transcripts and recognition sequences, the KH domain, known functions of Khdl, and the phenotypes it coordinates. My work represents the first application of CLIP to budding yeast, and the growing understanding of RNA-binding proteins in this organism facilitated the placement of Khdl into its posttranscriptional regulatory network. While many questions remain regarding the role Khdl plays in regulating cellular activities, this thesis addresses its direct role in key processes.

Book Dissertation Abstracts International

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 886 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Characterization of Novel RNA protein Regulatory Interactions in Saccharomyces Cerevisiae

Download or read book Characterization of Novel RNA protein Regulatory Interactions in Saccharomyces Cerevisiae written by Nikoleta Georgieva Tsvetanova and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The dynamic processes of a living cell depend on the coordinated temporal and spatial regulation of the many steps of gene expression. Transcription regulation is one control point of gene expression, and a gene can also be regulated post-transcriptionally, by RNA-binding proteins (RBPs). The biological significance of post-transcriptional regulation is especially evident in cases, where RBP binding controls the temporal precision of suppression and activation of important cellular stress responses. We developed a proteome-wide experimental approach for in vitro identification of novel RBPs and RNA-protein interactions in Saccharomyces cerevisiae. We found 12 novel RNA-binding proteins, the majority of which, surprisingly, are currently annotated as enzymes with roles in metabolic processes. We next used this proteomic approach to screen for proteins specifically interacting with the HAC1 RNA, which mediates activation of the yeast unfolded protein response (UPR). We found that HAC1 associated reproducibly with four small yeast GTPases, three of which are of the Ypt family of ras-GTPases. We further characterized one of them, the yeast Rab1 homolog Ypt1, and showed that Ypt1 interacted with unspliced HAC1 RNA only in the absence of ER stress. Selective Ypt1 depletion increased HAC1 RNA stability and expression, and also affected timely recovery from UPR. By developing and applying a novel proteomic approach for studying RNA-protein interactions, we established Ypt1 as an important regulator of HAC1 expression and UPR signaling. This unexpected protein-RNA interaction provides a biochemical mechanism for coordinating the key cellular processes of vesicle trafficking and ER homeostasis.

Book RNA binding Proteins as Regulators of Transcription and Axial Patterning During Xenopus Embryogenesis

Download or read book RNA binding Proteins as Regulators of Transcription and Axial Patterning During Xenopus Embryogenesis written by Caitlin DeJong and published by . This book was released on 2015 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA-binding proteins as regulators of transcription and axial patterning during Xenopus embryogenesis by Caitlin Suzanne DeJong Doctor of Philosophy in Molecular and Cell Biology University of California, Berkeley Professor Richard M. Harland, Chair The over-arching goal of this thesis is to expand our knowledge of the mechanisms by which one cell, a fertilized egg, develops into an organism composed of multiple cell types, each with different functions and behaviors. RNA-binding proteins have been identified as potent regulators of development and embryogenesis. The studies presented in this thesis illustrate the pleiotropic effects of RNA-binding proteins in Xenopus development and will focus specifically on two RNA-binding proteins that are maternally deposited and zygotically transcribed: TAF15 and DGCR8. TATA-binding protein-associated factor 15 (TAF15) belongs to the FET family of atypical RNA-binding proteins, which also includes Fused in sarcoma (Fus) and Ewing’s sarcoma (EWS). FET proteins were originally discovered as components of fusion oncogenes and are most noted for their implication in various cancers and neuromuscular degenerative diseases. However, little is known of the endogenous function of FET proteins. The diverse biological activities of the FET family proteins can be likened to a biological Swiss army knife; as these proteins contain domains for transcriptional activation, RNA-binding, DNA-binding, and function in both RNA Polymerase II-mediated transcription and pre-mRNA splicing. An exciting possibility is that the FET proteins may function to connect transcription and splicing. By employing the bioinformatics approach of RNA-sequencing, I generated a list of significant genes that are differentially expressed between uninjected and taf15 depleted embryos. From this analysis I found that TAF15 regulates target genes at both the transcriptional and post-transcriptional level. The studies that focus on the role of TAF15 in Xenopus development are described in chapters two and three of this thesis. In the second chapter of this thesis I describe studies that illustrate the novel concept that a protein can regulate the same set of target genes but through different molecular mechanisms. Both maternal and zygotic TAF15 regulate the expression of the transcripts fgfr4, isl1, and pax8. Interestingly, maternal TAF15 is required for the post-transcriptional regulation of fgfr4, isl1, and pax8, regulating the splicing of single introns within these transcripts, whereas zygotic TAF15 is required for the transcriptional regulation of these genes. Therefore, the studies described in chapter two demonstrate, for the first time, that a single protein can utilize a different molecular mechanism to control the same target genes and the use of these different mechanisms of action appears to be dependent on whether the protein is maternally deposited or zygotically transcribed. Single intron retention is a known mechanism to retain transcripts in the nucleus, preventing their translation. In chapter two of this thesis I provide evidence for the following model: in the absence of genome activation, before the zygotic genome is transcribed, maternal TAF15 cooperates with a splicing factor, the RNA-binding protein SRSF4, to regulate the splicing of single introns from transcripts. As a result, TAF15 and SRSF4 control the splicing of target genes and thus control the timing of transcript maturation and subsequent translation. This mechanism is logical as it provides a mechanism by which to spatially and temporally regulate gene expression in the absence of the ability to transcriptionally regulate genes. I further show evidence that following zygotic genome is activation, zygotic TAF15 activates target gene transcription, regulating genes at the transcriptional level, likely associating with the core promoter. The findings described in chapter two of this thesis are the first to show that a single protein can regulate the same gene targets but depending on the milieu of maternal of zygotic cofactors, regulates these targets via different underlying mechanisms. The variety of functional domains intrinsic to TAF15 supports the hypothesis that this atypical RNA-binding protein could operate as part of both a splicing and transcriptional complex. In the third chapter of this thesis I describe studies that illustrate the novel finding that TAF15 is required for dorsoventral patterning via the repression of ventx2.1. Ventx2 and BMP4 function in an autocatalytic positive feedback loop to specify ventral tissue and antagonize organizer function. Following taf15 depletion, ventx2.1 expression is expanded in the neural ectoderm and embryos exhibit a BMP overexpression phenotype: reduction in head, and dorsal, and posterior fin structures, with an increase in ventral tissue. Unlike the findings in chapter two, in this study, both maternal and zygotic TAF15 function to suppress ventx2.1 expression. These findings place TAF15 in the regulatory network of dorsoventral patterning and suggest that maternal and zygotic TAF15 control expression of ventx2.1 in a similar manner but do not rule out differential mechanisms of this control. Currently, it is unknown if TAF15 represses ventx2.1 expression directly or if TAF15 is required to activate a repressor of ventx2.1. In the fourth chapter of this thesis I describe studies that serve as a resource for future investigations into the role of microRNAs (miRNAs) in Xenopus development. DiGeorge syndrome critical region 8 (DGCR8) is a subunit of the microprocessor complex required for miRNA biogenesis. Unlike most members (e.g. Dicer, Argonaute2) of the RNA interference biogenesis pathway, DGCR8 is required specifically for miRNA biogenesis. Furthermore, unlike previous studies in mice and zebrafish that have depleted maternal dgcr8 throughout oogenesis to look at the role of miRNAs during embryogenesis, the antisense oligodeoxynucleotide (ODN) that I have designed can be used in host transfer assays to assess the effects of maternal dgcr8 depletion once oogenesis is complete, specifically during embryogenesis. Additionally, I have designed a splice-blocking morpholino (MO) antisense oligonucleotide that targets zygotic dgcr8 for depletion. Using these two tools (ODN and MO), the first studies can be performed that tease apart the role of maternal versus zygotic DGCR8 during embryogenesis. The work presented in this thesis exemplifies the value of carefully assessing biological functions of genes that are both maternally deposited and zygotically transcribed. The surprising finding that TAF15 utilizes distinct molecular mechanisms to control conserved target genes depending on whether this protein is maternally deposited or zygotically expressed demonstrates a new level of molecular complexity that future studies must address. Additionally, these studies further support the motivation to investigate RNA-binding proteins in development and disease as they continually prove to be multifaceted players in molecular biology.

Book Post transcriptional Regulation by the Pluripotency Associated RNA binding Protein LIN28

Download or read book Post transcriptional Regulation by the Pluripotency Associated RNA binding Protein LIN28 written by Melissa L. Wilbert and published by . This book was released on 2014 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of stem cell biology is moving forward at an unprecedented rate in part due to the discovery that adult somatic cells can be reprogrammed to a pluripotent stem cell like state. The factors first used in reprogramming were transcription factors such as OCT4, SOX2 and NANOG, and the RNA-binding protein LIN28. Like transcription factors, RNA-binding proteins (RBPs) control vast networks of gene targets to direct pathways in the cell; however, for RBPs this is accomplished through post-transcriptional binding to RNA transcripts. Only recently has it been possible to survey the transcripome-wide RNA binding interactions of a protein, through isolation of endogenous RBP-RNA complexes paired with high-throughput sequencing technologies. Using cross-linking followed by immunoprecipitation of protein-RNA complexes and sequencing of isolated transcripts (CLIP-seq) we have identified LIN28 binding sites throughout the human transcriptome. The resolution of our data enabled us to define characteristic LIN28 mRNA interactions at GGAGA rich motifs within unpaired regions of hairpin loops. This binding pattern mimics interactions described for LIN28 binding within let-7 family microRNA precursors. The ability to consider LIN28 targets on a global scale enabled the identification of RNA processing factors, in particular splicing factors, as prevalent functions encoded by LIN28 bound RNAs. This information helped to accurately predict which of the thousands of LIN28 targets would be functionally regulated. We found evidence that LIN28 increases the protein production of splicing factors resulting in massive rearrangement of RNA transcripts through downstream splicing changes. Subsequent transcriptome-wide studies of LIN28 have confirmed these findings despite differences in the pool of direct targets defined by individual reports. Taken together, we understand that LIN28 can bind to a wide network of transcripts, influencing development through these direct RNA interactions and via downstream effects. Combinatorial approaches in the study of LIN28 using changes in RNA-levels, protein production, strength of CLIP-seq binding, and ontological classification of gene targets have extracted meaningful information about mechanisms of LIN28 regulation. We expect that application of similar methods will enable studies of additional RBPs. For example, in the study of other stem cell enriched proteins like the IGFII-mRNA binding proteins (IG2BP or IMP). Furthermore, the overlap of other regulatory networks hold promise of highlighting novel hubs of regulation that may be exploited in reprogramming or directed differentiation. The next step is to use these connections to explain how genetic changes within an individual can affect RBP function and result in disease. We can apply in vitro modeling of development using directed differentiation to iteratively test how the connection of LIN28 to its target transcripts impacts its role in development and disease.

Book Identification and Characterization of C  Elegans RNAi Inheritance Machinery

Download or read book Identification and Characterization of C Elegans RNAi Inheritance Machinery written by George Frederick Spracklin IV and published by . This book was released on 2016 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt: Small RNAs can regulate gene expression in eukaryotes. During RNA interference (RNAi), small RNAs are bound by Argonaute proteins and act as guide molecules to silence cellular RNAs. In C. elegans, RNAi silencing can persist for 6-10 generations in the absence of the initial trigger (termed RNAi inheritance). RNAi inheritance requires the nuclear RNAi factors NRDE-1/-2/-4 highlighting the importance of co-transcriptional gene silencing and heterochromatin formation in heritable gene silencing by dsRNA. This thesis explores how gene silencing propagates across generations by identifying and characterizing cellular factors required for RNAi inheritance in the model organism C. elegans. Chapter 2 of this thesis identifies six novel components of the RNAi inheritance machinery whose sequence conservation provides insights into the molecular mechanism of RNAi inheritance and strengthens the correlation between RNAi inheritance and germline immortality. Chapter 2 also demonstrates that HRDE-2 promotes RNAi inheritance by coupling the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality.

Book Developmental Timing

    Book Details:
  • Author :
  • Publisher : Academic Press
  • Release : 2013-09-04
  • ISBN : 9780123969682
  • Pages : 0 pages

Download or read book Developmental Timing written by and published by Academic Press. This book was released on 2013-09-04 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new volume of Current Topics in Developmental Biology covers developmental timing, with contributions from an international board of authors. The chapters provide a comprehensive set of reviews covering such topics as the timing of developmental programs in Drosophila, temporal patterning of neural progenitors, and environmental modulation of developmental timing.

Book The Roles of RNA binding Proteins in the Developing Nervous System

Download or read book The Roles of RNA binding Proteins in the Developing Nervous System written by Jie Quan and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA-binding proteins are key players in post-transcriptional regulation of gene expression by orchestrating RNA fate from synthesis to decay. Hundreds of proteins with RNA-binding capacity have been identified so far, yet only a small fraction has been functionally characterized and presumably many more RNA-binding proteins await discovery. The roles of RNA-binding proteins in the nervous system are of particular interest because accumulative evidence has linked RNA-based mechanisms to neural development, maintenance and repair. Here, the three RNA-binding proteins under study are IGF-II mRNA binding proteins IMP-1 and IMP-2, known to be involved in mRNA localization, translational control and stability, and adenomatous polyposis coli (APC), identified as a novel RNA-binding protein.