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Articles 1 - 30 of 45

Full-Text Articles in Molecular Biology

Synergistic Assembly Of Human Pre-Spliceosomes Across Introns And Exons, Joerg E. Braun, Larry J. Friedman, Jeff Gelles, Melissa J. Moore Jun 2018

Synergistic Assembly Of Human Pre-Spliceosomes Across Introns And Exons, Joerg E. Braun, Larry J. Friedman, Jeff Gelles, Melissa J. Moore

RNA Therapeutics Institute Publications

Most human genes contain multiple introns, necessitating mechanisms to effectively define exons and ensure their proper connection by spliceosomes. Human spliceosome assembly involves both cross-intron and cross-exon interactions, but how these work together is unclear. We examined in human nuclear extracts dynamic interactions of single pre-mRNA molecules with individual fluorescently tagged spliceosomal subcomplexes to investigate how cross-intron and cross-exon processes jointly promote pre-spliceosome assembly. U1 subcomplex bound to the 5' splice site of an intron acts jointly with U1 bound to the 5' splice site of the next intron to dramatically increase the rate and efficiency by which U2 subcomplex ...


All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer May 2018

All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer

University of Massachusetts Medical School Faculty Publications

Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted forin vivo genome engineering applications: SpyCas9, SauCas9 and CjeCas9. However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome. Here, we present an additional in vivo editing platform using Neisseria ...


Small Rnas Gained During Epididymal Transit Of Sperm Are Essential For Embryonic Development In Mice, Colin C. Conine, Fengyun Sun, Lina Song, Jaime A. Rivera-Perez, Oliver J. Rando Apr 2018

Small Rnas Gained During Epididymal Transit Of Sperm Are Essential For Embryonic Development In Mice, Colin C. Conine, Fengyun Sun, Lina Song, Jaime A. Rivera-Perez, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) vs. distal (cauda) epididymis, then characterized development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, and subsequently implant inefficiently and fail soon after implantation. Remarkably, microinjection ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban Apr 2018

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...


Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler May 2017

Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler

Dissertations

Coenzyme A is an indispensable molecule in all known life with roles in metabolism, gene regulation, and macromolecule synthesis. As CoA is derived from RNA itself, it’s incorporation into RNA by in vitro methods has proven useful in research probing the origin of life based on the RNA World theory. The discovery in contemporary bacteria of RNA modified with CoA, however, provided an unexpected twist to previously well-characterized bacterial systems. The identity of sequences associated with CoA-RNA has been elusive since their discovery in 2009 based on the difficulties in isolation while maintaining RNA quality. The aim of this ...


The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham Jan 2017

The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham

Undergraduate Honors Theses

In as many as 70% of colorectal cancer cell (CRC) lines, there is a deletion of a chromosomal region, 18q21, which contains the Deleted in Colorectal Carcinoma (DCC) gene (Mehlen & Fearon, 2004). In adult cells, this single transmembrane receptor plays a role in both cell proliferation and cell death, thereby making it a promising candidate gene for the pathogenesis of colorectal cancer. It has been observed that alternative splicing of the DCC can affect its activity and that alternative splicing of DCC can be disrupted in cancer (Leggere et al., 2016; Reale et al., 1994). In this experiment, we sought to determine the association of alternative splicing of the DCC with colorectal cancer in cells without the deletion of the 18q21 region. By extracting RNA from 35 CRC cell lines and performing RT-PCR, we observed levels of the two DCC isoforms compared to normal adult colon cells. In this way, we determined that 29 of 35 CRC cell lines had altered ...


Elucidating Nucleic Acid Binding Properties Of Polycomb Repressive Complex 2, Richard D. Paucek Jan 2017

Elucidating Nucleic Acid Binding Properties Of Polycomb Repressive Complex 2, Richard D. Paucek

Undergraduate Honors Theses

Polycomb Repressive Complex 2 (PRC2) is a histone methyltransferase that specifically deposits mono-, di-, and tri-methylation marks onto chromatin. This activity triggers epigenetic silencing, a process critical for cell differentiation and maintenance of cellular identity. In mammalian cells, how PRC2 is recruited to target sites is unknown, but it is speculated that RNA, histone modifications, nucleosome architecture, and DNA elements all possess direct or indirect recruitment and regulatory roles. However, the relative binding affinity of PRC2 for these diverse biological substrates remains poorly understood. In the present study, the binding affinity of PRC2 for various RNAs and nucleosomes were tested ...


Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu Feb 2016

Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu

All Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in the stability ...


Novel Functions Of The Survival Motor Neuron Protein, Eric William Ottesen Jan 2016

Novel Functions Of The Survival Motor Neuron Protein, Eric William Ottesen

Graduate Theses and Dissertations

The Survival Motor Neuron (SMN) protein is a multi-functional protein that participates in a wide variety of critical pathways. Low levels of SMN cause spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. While the role of SMN in the assembly of small nuclear ribonucleoproteins (snRNPs) has been well characterized, many of its other diverse functions have not been thoroughly explored. Here, we examine the critical role of SMN in the growth and development of male mammalian sex organs. We show that low levels of SMN in a mild mouse model of SMA cause impaired testis development ...


The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh Jan 2016

The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh

Publicly Accessible Penn Dissertations

PSF is a ubiquitously expressed and essential nuclear protein that influences many aspects of the genome maintenance and gene expression pathways. Although previous studies have identified numerous protein cofactors and nucleic acid targets of PSF, insufficient work has been done to understand how it is regulated to accomplish its various functions in a coordinated manner. Previous research in the Lynch laboratory demonstrated that, in T cells, PSF is a downstream target of the serine/threonine kinase GSK3. Phosphorylation of PSF T687 by GSK3 promotes interaction of PSF with another multifunctional nuclear factor, TRAP150. This interaction prevents PSF from binding RNA ...


Genome-Wide Approaches To Study Rna Secondary Structure, Nathan Daniel Berkowitz Jan 2016

Genome-Wide Approaches To Study Rna Secondary Structure, Nathan Daniel Berkowitz

Publicly Accessible Penn Dissertations

The central hypothesis of molecular biology depicts RNA as an intermediary conveyor of genetic information. RNA is transcribed from DNA and translated to proteins, the molecular machines of the cell. However, many RNAs do not encode protein and instead function as molecular machines themselves. The most famous examples are ribosomal RNAs and transfer RNAs, which together form the core translational machinery of the cell. Many other non-coding RNAs have been discovered including catalytic and regulatory RNAs. In many cases RNA function is tightly linked to its secondary structure, which is the collection of hydrogen bonds between complimentary RNA sequences that ...


Optimizing Rna Library Preparation To Redefine The Translational Status Of 80s Monosomes: A Dissertation, Erin E. Heyer Oct 2015

Optimizing Rna Library Preparation To Redefine The Translational Status Of 80s Monosomes: A Dissertation, Erin E. Heyer

GSBS Dissertations and Theses

Deep sequencing of strand-specific cDNA libraries is now a ubiquitous tool for identifying and quantifying RNAs in diverse sample types. The accuracy of conclusions drawn from these analyses depends on precise and quantitative conversion of the RNA sample into a DNA library suitable for sequencing. Here, we describe an optimized method of preparing strand-specific RNA deep sequencing libraries from small RNAs and variably sized RNA fragments obtained from ribonucleoprotein particle footprinting experiments or fragmentation of long RNAs. Because all enzymatic reactions were optimized and driven to apparent completion, sequence diversity and species abundance in the input sample are well preserved ...


A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder Sep 2015

A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder

Sean P. Ryder

Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside ...


A Lipopolysaccharide-Induced Dna-Binding Protein For A Class Ii Gene In B Cells Is Distinct From Nf-Kappa B, Ellen M. Gravallese, Mark R. Boothby, Cynthia M. Smas, Laurie H. Glimcher Apr 2015

A Lipopolysaccharide-Induced Dna-Binding Protein For A Class Ii Gene In B Cells Is Distinct From Nf-Kappa B, Ellen M. Gravallese, Mark R. Boothby, Cynthia M. Smas, Laurie H. Glimcher

Ellen M. Gravallese

Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant ...


Towards A Unified Model Of Sperm Chromatin Structure, Graham Johnson Jan 2015

Towards A Unified Model Of Sperm Chromatin Structure, Graham Johnson

Wayne State University Dissertations

Sperm possess several layers of information that are delivered to the oocyte alongside the paternal DNA. Examples of potential sperm borne molecular cues of probable use to the embryo include RNAs and local and global chromatin structure. To identify candidate sperm RNAs that likely reach the oocyte cytoplasm following fertilization patterns of transcript compartmentalization in the mature gamete were identified. Though all sperm RNAs exhibited a preferential peripheral enrichment, a subset of RNAs were identified in which this trend was reduced. These RNAs are thought to be embedded with perinuclear theca and are correlated with late spermatogenic transcription. Malat1, a ...


Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr. Jan 2015

Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr.

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

miRNAs are small non-coding RNAs, approximately 22 nucleotide in length, that mediate post-transcriptional repression of target mRNAs. Since their discovery in mammals in the early 2000s, miRNAs have been intensely studied and determined to be an important mechanism to regulate gene expression in diverse biological processes. In human cancers, miRNAs are known to act as tumor suppressors or oncogenes and are being actively explored as a possible mechanism for therapeutic intervention. In the mouse, multistage skin carcinogenesis is a well-established model for studying tumor development however the functions of miRNAs in this model are poorly understood.

The Ras oncogene was ...


Purine Riboswitches: A Model System For The Study Of Rna Structural Biology And A Platform For The Advancement Of Synthetic Rna Technologies, Joan Gabriel Marcano-Velázquez Jan 2015

Purine Riboswitches: A Model System For The Study Of Rna Structural Biology And A Platform For The Advancement Of Synthetic Rna Technologies, Joan Gabriel Marcano-Velázquez

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

The scientific discipline known as synthetic biology aims to develop a set of tools and engineering principles to design artificial biological systems for the production of commodity chemicals like biofuels and therapeutics. A variety of bacterial non-coding RNAs named riboswitches, are particularly attractive for the field of synthetic biology for their ability to create intricate tertiary structures capable of binding a small molecule metabolite and translating this event into the regulation of gene expression. Riboswitches have been studied with a variety of biophysical and biochemical techniques that have provided a wealth of information useful in the rational design of synthetic ...


Regulation Of Synaptogenesis By The Mirna Pathway And Fmr/P Bodies, Jacqueline Rochelle Furlong Jan 2015

Regulation Of Synaptogenesis By The Mirna Pathway And Fmr/P Bodies, Jacqueline Rochelle Furlong

Electronic Theses and Dissertations

Post-transcriptional regulation of mRNA is facilitated by different mechanisms, such as microRNA (miRNA) induced gene silencing or fragile X mental retardation protein (FMRP) mediated repression either independent of or acting through cytoplasmic RNA Processing bodies (P bodies). DPTP99A, Lar, and Wg have known functions during synaptogenesis and may be targets of miR-8. Here, we provide evidence that miR-8 regulates DPTP99A in vitro. Non-endogenous miR-8 expressed using an UAS driver regulates Lar. Endogenous miR-8 may regulate DPTP99A in vivo. Here we show that FMRP is capable of colocalizing with the P body components: DCP1, HPat, and Me31B, but not CCR4. We ...


Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar Jan 2015

Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar

Publicly Accessible Penn Dissertations

Human cells are dynamic: they grow, replicate their genetic information (DNA), and divide. Clonal populations of cells can display marked heterogeneity in size, leading to significant variability in the ratio of DNA to cellular volume. Despite this variability, cells must maintain a constant concentration of RNA and protein, produced from DNA, to ensure proper functionality. How do larger cells produce more output from the same amount of DNA? How do cells that have replicated their DNA prior to cellular division produce the same output as before? Using RNA fluorescence in situ hybridization (RNA FISH), we visualize and count individual RNA ...


Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton Oct 2014

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.


A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Dissertation, Carina C. Clingman Sep 2014

A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Dissertation, Carina C. Clingman

GSBS Dissertations and Theses

All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second-­‐messenger systems. In bacteria, metabolites also affect post-­‐transcriptional regulatory mechanisms, but there are only a few isolated examples of this regulation in eukaryotes. Here, I present evidence that RNA-­‐binding by the stem cell translation regulator Musashi-­‐1 (MSI1) is allosterically inhibited by 18-­‐22 carbon ω-­‐9 monounsaturated fatty acids. The fatty acid binds to the N-­‐terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi ...


Identification Of Molecular Determinants That Shift Co- And Post-Translational N-Glycosylation Kinetics In Type I Transmembrane Peptides: A Dissertation, Heidi L. H. Malaby Apr 2014

Identification Of Molecular Determinants That Shift Co- And Post-Translational N-Glycosylation Kinetics In Type I Transmembrane Peptides: A Dissertation, Heidi L. H. Malaby

GSBS Dissertations and Theses

Asparagine (N)-linked glycosylation occurs on 90% of membrane and secretory proteins and drives folding and trafficking along the secretory pathway. The N-glycan can be attached to an N-X-T/S-Y (X,Y ≠ P) consensus site by one of two oligosaccharyltransferase (OST) STT3 enzymatic isoforms either during protein translation (co-translational) or after protein translation has completed (post-translational). While co-translational N-glycosylation is both rapid and efficient, post-translational N-glycosylation occurs on a much slower time scale and, due to competition with protein degradation and forward trafficking, could be detrimental to the success of a peptide heavily reliant on post-translational N-glycosylation. In evidence, mutations ...


Characterization Of The Rna Binding And Rna Degrading Subunits Of The Eukaryotic Exosome, Borislava Tsanova Dec 2013

Characterization Of The Rna Binding And Rna Degrading Subunits Of The Eukaryotic Exosome, Borislava Tsanova

UT GSBS Dissertations and Theses (Open Access)

The exosome is an essential complex of ten proteins involved in the processing and degradation of many RNAs in the cell. These include various stable RNAs, mRNAs, and aberrant transcripts both in the nucleus and in the cytoplasm.

In this work I characterize the three members of the exosome “cap”, the RNA binding proteins Rrp4, Rrp40, and Csl4. I determine that in spite of their structural similarity, they each have a unique essential role. Second, I determine that two of the cap proteins Rrp4 and Rrp40 have a role in bridging subunits of the PH ring of the exosome. The ...


Nucleic Acid Determinants Of Cytosine Deamination By Aid/Apobec Enzymes In Immunity And Epigenetics, Christopher Nabel Jan 2013

Nucleic Acid Determinants Of Cytosine Deamination By Aid/Apobec Enzymes In Immunity And Epigenetics, Christopher Nabel

Publicly Accessible Penn Dissertations

A multitude of functions have evolved around cytosine within DNA, endowing the base with physiological significance beyond simple information storage. This versatility arises from enzymes that chemically modify cytosine to expand the potential of the genome. Cytosine can be methylated, oxidized, and deaminated to modulate transcription and immunologic diversity. At the crossroads of these modifications sit the AID/APOBEC family deaminases, which accomplish diverse functions ranging from antibody diversification and innate immunity to mRNA editing. In addition, novel roles have been proposed in oncogenesis and DNA demethylation. Behind these established and emerging physiologic activities remain important questions about the substrate ...


Methods In And Applications Of The Sequencing Of Short Non-Coding Rnas, Paul Ryvkin Jan 2013

Methods In And Applications Of The Sequencing Of Short Non-Coding Rnas, Paul Ryvkin

Publicly Accessible Penn Dissertations

Short non-coding RNAs are important for all domains of life. With the advent of modern molecular biology their applicability to medicine has become apparent in settings ranging from diagonistic biomarkers to therapeutics and fields ranging from oncology to neurology. In addition, a critical, recent technological development is high-throughput sequencing of nucleic acids. The convergence of modern biotechnology with developments in RNA biology presents opportunities in both basic research and medical settings. Here I present two novel methods for leveraging high-throughput sequencing in the study of short non-coding RNAs, as well as a study in which they are applied to Alzheimer ...


Characterization Of New Factors In The 18s Nonfunctional Ribosomal Rna Decay Pathway In S. Cerevisiae: A Dissertation, Christopher N. Merrikh Mar 2012

Characterization Of New Factors In The 18s Nonfunctional Ribosomal Rna Decay Pathway In S. Cerevisiae: A Dissertation, Christopher N. Merrikh

GSBS Dissertations and Theses

The molecular biology revolution of the 1960s has given rise to an enormous body of literature describing, in great detail, the inner workings of the cell. Over the course of the past 50 years, and countless hours at the bench, biologists have used the implications of basic research to produce vaccines, antibiotics, and other therapies that have improved both the quality and duration of our lives. Despite these incredible advances, basic questions remain unanswered. In even the simplest model organism, hundreds of essential genes have never been studied. Moreover, the central dogma of molecular biology—DNA to RNA to Protein ...


Global And Specific Controls Of Protein Synthesis In Hibernators, Peipei Pan Dec 2011

Global And Specific Controls Of Protein Synthesis In Hibernators, Peipei Pan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mammalian hibernation is a highly dynamic physiological process that is composed of a series of torpor bouts, wherein hibernators oscillate between periods of torpor and interbout arousal. Although normally vital to homeostasis, many energetically consumptive processes such as translation or protein synthesis are virtually ceased during hibernation. Earlier studies indicated that protein synthesis had fallen to almost negligible levels. Cap-dependent initiation of translation is well regulated by eukaryotic translation initiation factor 4E (eIF4E) and its binding partner eIF4E-binding protein 1 (4E-BP1) when hibernators cycle in and out the torpor state. Herein, I investigated well-characterized regulatory mechanisms of global and specific ...


A Brain-Derived Mecp2 Complex Supports A Role For Mecp2 In Rna Processing, Steven W. Long, Jenny Y. Y. Ooi, Peter M. Yau, Peter L. Jones Oct 2011

A Brain-Derived Mecp2 Complex Supports A Role For Mecp2 In Rna Processing, Steven W. Long, Jenny Y. Y. Ooi, Peter M. Yau, Peter L. Jones

Peter Jones Lab Publications

Mutations in MECP2 (methyl-CpG-binding protein 2) are linked to the severe postnatal neurodevelopmental disorder RTT (Rett syndrome). MeCP2 was originally characterized as a transcriptional repressor that preferentially bound methylated DNA; however, recent results indicate MeCP2 is a multifunctional protein. MeCP2 binding is now associated with certain expressed genes and involved in nuclear organization as well, indicating that its gene regulatory function is context-dependent. In addition, MeCP2 is proposed to regulate mRNA splicing and a mouse model for RTT shows aberrant mRNA splicing. To further understand MeCP2 and potential roles in RTT pathogenesis, we have employed a biochemical approach to identify ...


Ku Can Contribute To Telomere Lengthening In Yeast At Multiple Positions In The Telomerase Rnp, David C. Zappulla, Karen J. Goodrich, Julian R. Arthur, Lisa A. Gurski, Elizabeth M. Denham, Anne E. Stellwagen, Thomas R. Cech Dec 2010

Ku Can Contribute To Telomere Lengthening In Yeast At Multiple Positions In The Telomerase Rnp, David C. Zappulla, Karen J. Goodrich, Julian R. Arthur, Lisa A. Gurski, Elizabeth M. Denham, Anne E. Stellwagen, Thomas R. Cech

Chemistry & Biochemistry Faculty Contributions (1986-2018)

Unlike ribonucleoprotein complexes that have a highly ordered overall architecture, such as the ribosome, yeast telomerase appears to be much more loosely constrained. Here, we investigate the importance of positioning of the Ku subunit within the 1157-nt yeast telomerase RNA (TLC1). Deletion of the 48-nt Ku-binding hairpin in TLC1 RNA (tlc1Δ48) reduces telomere length, survival of cells with gross chromosomal rearrangements, and de novo telomere addition at a broken chromosome end. To test the function of Ku at novel positions in the telomerase RNP, we reintroduced its binding site into tlc1Δ48 RNA at position 446 or 1029. We found that ...


Molecular Characterisation Of Canine Nonsteroidal Anti-Inflammatory Drug-Activated Gene (Nag-1), K Yamaguchi, Nichelle Whitlock, Jason Liggett, Alfred Legendre, Michael Fry, Seung Baek Dec 2010

Molecular Characterisation Of Canine Nonsteroidal Anti-Inflammatory Drug-Activated Gene (Nag-1), K Yamaguchi, Nichelle Whitlock, Jason Liggett, Alfred Legendre, Michael Fry, Seung Baek

Alfred M Legendre DVM, MS, DACVIM

Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor beta superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARgamma ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and ...