Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel

Dissertations, Theses, and Capstone Projects

Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …

Defining Rna Oligonucleotides That Reverse Deleterious Phase Transitions Of Rna-Binding Proteins With Prion-Like Domains., Lin Guo, Jacob Mann, Jocelyn Mauna, Katie Copley, Hejia Wang, Jack Rubien, Cristian Bergmann, Jenny Carey, Jessica Merjane, Marilyn Ngo, Jiazhen Xu, Hana Odeh, Jiabei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin Kim, Anastasia Murthy, Tapas Paul, Bede Portz, Amanda Gleixner, Zamia Diaz, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric Huang, Alessandra Chesi, Nicolas Fawzi, Sua Myong, Christopher Donnelly, James Shorter

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs that prevent FUS fibrillization by promoting liquid phases and distinct short RNAs that prevent and reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. We define a short RNA that dissolves cytoplasmic FUS aggregates, restores nuclear FUS, and mitigates FUS toxicity in optogenetic models and ALS …

Optimizing Endothelial Cell Specific Polymersome-Based Atheroprotective Therapies, Ally C. Brawner

All Theses

Atherosclerotic cardiovascular disease is the number one cause of death in the United States and the world. Every year, billions of dollars are spent in the US alone for direct treatments of this disease, especially on prescription medicines like statins. However, these medications have been unable to curtail global mortality rates, partially because they do not target the entirety of atherosclerotic pathophysiology. A key area of this pathophysiology is that atheroprone arteries typically include pro-inflammatory endothelial cells that exhibit decreased levels of apoAI-mediated cholesterol efflux and an increased release of adhesion molecules, such as VCAM-1. The objective of my project …

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

Screening For Penicillin G Acylase (Pga)-Producing Bacteria And Gene Cloning Using Degenerate Oligonucleotide Primed-Pcr, Masdalifah Masdalifah, Sri Rezeki Wulandari, Gabriela Christy Sabbathini, Maria Ulfah, Dini Achnafani, Ahmad Wibisana, Feronika Heppy Sriherfyna, Is Helianti, Niknik Nurhayati

Makara Journal of Science

The growing concern over antibiotic resistance has driven global efforts to explore innovative solutions, including the use of Penicillin G acylase (PGA) to produce semisynthetic β-lactam antibiotics. This study screened four potential in-tracellular PGA-producing bacteria: Alcaligenes faecalis InaCC B444 (AfPGA), Kluyvera cryocrescens InaCC B850 (KcPGA), Providencia rettgeri InaCC B25 (Pr25PGA), and P. rettgeri InaCC B466 (Pr466PGA). Penicillin G Acylase encoding genes (pgas) were isolated from them using a Degenerate Oligonucleotide Primed-PCR (DOP-PCR) approach and sequenced. Microbiological assays confirmed all tested crude extracts to exhibit inhibitory effects. Penicillin G was used for evaluating hydrolytic activity and 6-Amino Penicillanic Acid (6-APA) coupled …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …

Single Dual-Specific Anti-Pd-L1/Tgf-Β Antibody Synergizes With Chemotherapy As Neoadjuvant Treatment For Pancreatic Ductal Adenocarcinoma: A Preclinical Experimental Study, Haoxiang Zhang, Jiaoshun Chen, Jianwei Bai, Jing Zhang, Shaoyi Huang, Liang Zeng, Pengfei Zhou, Qiang Shen, Tao Yin

School of Medicine Faculty Publications

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-β) and programmed cell death 1 ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP …

Modifying Peptide/Lipid-Associated Nucleic Acids (Planas) For Crispr/Cas9 Ribonucleoprotein Delivery, Abdulelah Alhazza, Parvin Mahdipoor, Ryley Hall, Arthur Manda, Sandeep Lohan, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

With the first reports on the possibility of genome editing by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas)9 surfacing in 2005, the enthusiasm for protein silencing via nucleic acid delivery experienced a resurgence following a period of diminished enthusiasm due to challenges in delivering small interfering RNAs (siRNA), especially in vivo. However, delivering the components necessary for this approach into the nucleus is challenging, maybe even more than the cytoplasmic delivery of siRNA. We previously reported the birth of peptide/lipid-associated nucleic acids (PLANAs) for siRNA delivery. This project was designed to investigate the efficiency of …

Hybridization Kinetics Of Four-Way Junctions Localized On A Dna Scaffold, Katherine N. Taylor

Honors Undergraduate Theses

DNA computing is an ever-growing field with scientists trying to design structures that optimize logic gate communication to develop fast, biologically compatible, computational structures. We hypothesize that by using the principles of DNA computing, it is possible to design a DNA tile capable of studying localized DNA hybridization that can differentiate between oligonucleotides of different structural conformations. This includes synthetically manipulating DNA into a nanostructure that can perform Boolean logic functions to calculate the different rates of hybridization. To test our hypothesis, we designed a DNA Tile that incorporated a 4WJ using YES logic. Linear and hairpin single-stranded (ss) DNA …

Environmental Exposures And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

In recent years, research into air pollution has shown that exposure to certain components in air pollution, primarily PM2.5 can accelerate biological aging and thereby lead to increased susceptibility to multiple diseases. We hypothesize that prolonged exposure to air pollutants can result in premature aging leading to extensive tissue dysfunction and susceptibility to diseases. To examine this, we exposed mice to PM2.5 for 9, 15, and 21 days, then measured the telomere lengths, cellular senescence, and histone methylation patterns of multiple cell types. We found consistently increased telomere attrition, cellular senescence and advanced age-consistent histone methylation patterns in groups exposed …

Purification And Biochemical Characterization Of The Dna Binding Domain Of The Nitrogenase Transcriptional Activator Nifa From Gluconacetobacter Diazotrophicus, Heidi G. Standke, Lois Kim, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

NifA is a σ⁵⁴ activator that turns on bacterial nitrogen fixation under reducing conditions and when fixed cellular nitrogen levels are low. The redox sensing mechanism in NifA is poorly understood. In α- and β-proteobacteria, redox sensing involves two pairs of Cys residues within and immediately following the protein’s central AAA⁺ domain. In this work, we examine if an additional Cys pair that is part of a C(X)5 C motif and located immediately upstream of the DNA binding domain of NifA from the α-proteobacterium Gluconacetobacter diazotrophicus (Gd) is involved in redox sensing. We hypothesize that the …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

The Developing Effects Of Potassium Ferricyanide On Tetrahymena, Katelyn Coronell

Whittier Scholars Program

Potassium Cyanide is a highly toxic chemical asphyxiant that interferes with the body's ability to use oxygen, typically by directly affecting the body by ingestion, inhalation, skin contact, or eye contact(CDC, 2011). Due to its high toxicity, the main effect that leads to the downfall of the organism begins with the cessation of aerobic metabolism; it does this by cyanide binding to the ferric ions and inhibiting cytochrome oxidase within the mitochondria (Zhang, 2015). There are no physical dangers the substance causes. Although, there are many chemical dangers. If used at temperatures higher than 70℉ The substance may produce toxic …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke

Senior Honors Theses

The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy+diagnostic) …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Modulation Of Escherichia Coli Translation By The Specific Inactivation Of TrnaGly Under Oxidative Stress, Lorenzo Eugenio Leiva, Andrea Pincheira, Sara Elgamal, Sandra D. Kienast, Verónica Bravo, Johannes Leufken, Daniela Gutiérrez, Sebastian A. Leidel, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial oxidative stress responses are generally controlled by transcription factors that modulate the synthesis of RNAs with the aid of some sRNAs that control the stability, and in some cases the translation, of specific mRNAs. Here, we report that oxidative stress additionally leads to inactivation of tRNA^Gly in Escherichia coli, inducing a series of physiological changes. The observed inactivation of tRNA^Gly correlated with altered efficiency of translation of Gly codons, suggesting a possible mechanism of translational control of gene expression under oxidative stress. Changes in translation also depended on the availability of glycine, revealing a mechanism whereby bacteria …

Translational Regulation Of Environmental Adaptation In Bacteria, Rodney Tollerson Ii, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacteria must rapidly respond to both intracellular and environmental changes to survive. One critical mechanism to rapidly detect and adapt to changes in environmental conditions is control of gene expression at the level of protein synthesis. At each of the three major steps of translation—initiation, elongation, and termination—cells use stimuli to tune translation rate and cellular protein concentrations. For example, changes in nutrient concentrations in the cell can lead to translational responses involving mechanisms such as dynamic folding of riboswitches during translation initiation or the synthesis of alarmones, which drastically alter cell physiology. Moreover, the cell can fine-tune the levels …