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Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev 2020 University of Connecticut

Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev

Open Access Articles

Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several biological systems. The long intergenic RNA-erythroid pro-survival (lincRNA-EPS) has been shown to play a critical role in restraining inflammatory gene expression. However, the function of lincRNA-EPS during bacterial infections remains unknown. Here, we demonstrate that following infection with the intracellular bacterium Listeria monocytogenes, both mouse macrophages and dendritic cells lacking lincRNA-EPS exhibit an enhanced expression of proinflammatory cytokine genes, as well as an increased expression of the inducible nitric oxide synthase (iNos) and nitric oxide (NO) production. Importantly, we found that lincRNA-EPS(-/-) mice intraperitoneally infected with ...


Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency (Maple Syrup Urine Disease): Treatment, Biomarkers, And Outcomes, Kevin A. Strauss 2020 University of Massachusetts Medical School

Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency (Maple Syrup Urine Disease): Treatment, Biomarkers, And Outcomes, Kevin A. Strauss

Open Access Articles

Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain alpha-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard ...


Reporter Assays For Ebola Virus Nucleoprotein Oligomerization, Virion-Like Particle Budding, And Minigenome Activity Reveal The Importance Of Nucleoprotein Amino Acid Position 111, Aaron E. Lin, William E. Diehl, Yingyun Cai, Courtney L. Finch, Chidiebere Akusobi, Robert N. Kirchdoerfer, Laura Bollinger, Stephen F. Schaffner, Elizabeth A. Brown, Erica Ollmann Saphire, Kristian G. Andersen, Jens H. Kuhn, Jeremy Luban, Pardis C. Sabeti 2020 Harvard Medical School

Reporter Assays For Ebola Virus Nucleoprotein Oligomerization, Virion-Like Particle Budding, And Minigenome Activity Reveal The Importance Of Nucleoprotein Amino Acid Position 111, Aaron E. Lin, William E. Diehl, Yingyun Cai, Courtney L. Finch, Chidiebere Akusobi, Robert N. Kirchdoerfer, Laura Bollinger, Stephen F. Schaffner, Elizabeth A. Brown, Erica Ollmann Saphire, Kristian G. Andersen, Jens H. Kuhn, Jeremy Luban, Pardis C. Sabeti

Open Access Articles

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]). The Ebola virus nucleoprotein (NP) plays multiple essential roles during the viral life cycle, yet few tools exist to study the protein under BSL-2 or equivalent containment. Therefore, we adapted reporter assays to measure NP oligomerization and virion-like particle (VLP) production in live cells and further measured transcription and replication using established minigenome assays. As a proof-of-concept, we examined the NP-R111C substitution, which emerged during the 20132016 Western African ...


Glycan Profiles Of Gp120 Protein Vaccines From Four Major Hiv-1 Subtypes Produced From Different Host Cell Lines Under Non-Gmp Or Gmp Conditions, Shixia Wang, Yegor Voronin, Peng Zhao, Mayumi Ishihara, Nickita Mehta, Mindy Porterfield, Yuxin Chen, Christopher Bartley, Guangnan Hu, Dong Han, Lance Wells, Michael Tiemeyer, Shan Lu 2020 University of Massachusetts Medical School

Glycan Profiles Of Gp120 Protein Vaccines From Four Major Hiv-1 Subtypes Produced From Different Host Cell Lines Under Non-Gmp Or Gmp Conditions, Shixia Wang, Yegor Voronin, Peng Zhao, Mayumi Ishihara, Nickita Mehta, Mindy Porterfield, Yuxin Chen, Christopher Bartley, Guangnan Hu, Dong Han, Lance Wells, Michael Tiemeyer, Shan Lu

Open Access Articles

Envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is an important target for the development of an HIV vaccine. Extensive glycosylation of Env is an important feature that both protects the virus from antibody responses and serves as a target for some highly potent broadly neutralizing antibodies. Therefore, analysis of glycans on recombinant Env proteins is highly significant. Here we present glycosylation profiles of recombinant gp120 proteins from four major clades of HIV-1 (A, B, C, and AE) produced either as research-grade material in 293 and CHO cells or as two independent lots of clinical material under GMP ...


Real-Time Analysis Of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics, Natasha D. Durham, Angela R. Howard, Ramesh Govindan, Fernando Senjobe, J. Maximilian Fels, William E. Diehl, Jeremy Luban, Kartik Chandran, James B. Munro 2020 University of Massachusetts Medical School

Real-Time Analysis Of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics, Natasha D. Durham, Angela R. Howard, Ramesh Govindan, Fernando Senjobe, J. Maximilian Fels, William E. Diehl, Jeremy Luban, Kartik Chandran, James B. Munro

Open Access Articles

The Ebola virus (EBOV) envelope glycoprotein (GP) mediates the fusion of the virion membrane with the membrane of susceptible target cells during infection. While proteolytic cleavage of GP by endosomal cathepsins and binding of the cellular receptor Niemann-Pick C1 protein (NPC1) are essential steps for virus entry, the detailed mechanisms by which these events promote membrane fusion remain unknown. Here, we applied single-molecule Forster resonance energy transfer (smFRET) imaging to investigate the structural dynamics of the EBOV GP trimeric ectodomain, and the functional transmembrane protein on the surface of pseudovirions. We show that in both contexts, pre-fusion GP is dynamic ...


Airway Epithelial Specific Deletion Of Jun-N-Terminal Kinase 1 Attenuates Pulmonary Fibrosis In Two Independent Mouse Models, Jos L. van der Velden, John F. Alcorn, David G. Chapman, Lennart K. A. Lundblad, Charles G. Irvin, Roger J. Davis, Kelly Butnor, Yvonne M. W. Janssen-Heininger 2020 University of Vermont

Airway Epithelial Specific Deletion Of Jun-N-Terminal Kinase 1 Attenuates Pulmonary Fibrosis In Two Independent Mouse Models, Jos L. Van Der Velden, John F. Alcorn, David G. Chapman, Lennart K. A. Lundblad, Charles G. Irvin, Roger J. Davis, Kelly Butnor, Yvonne M. W. Janssen-Heininger

Open Access Articles

The stress-induced kinase, c-Jun-N-terminal kinase 1 (JNK1) has previously been implicated in the pathogenesis of lung fibrosis. However, the exact cell type(s) wherein JNK1 exerts its pro-fibrotic role(s) remained enigmatic. Herein we demonstrate prominent activation of JNK in bronchial epithelia using the mouse models of bleomycin- or AdTGFbeta1-induced fibrosis. Furthermore, in lung tissues of patients with idiopathic pulmonary fibrosis (IPF), active JNK was observed in various regions including type I and type II pneumocytes and fibroblasts. No JNK activity was observed in adjacent normal tissue or in normal control tissue. To address the role of epithelial JNK1, we ...


Structure Of The Vesicular Stomatitis Virus L Protein In Complex With Its Phosphoprotein Cofactor, Simon Jenni, Louis-Marie Bloyet, Ruben Diaz-Avalos, Bo Liang, Sean P.J. Whelan, Nikolaus Grigorieff, Stephen C. Harrison 2020 Harvard Medical School

Structure Of The Vesicular Stomatitis Virus L Protein In Complex With Its Phosphoprotein Cofactor, Simon Jenni, Louis-Marie Bloyet, Ruben Diaz-Avalos, Bo Liang, Sean P.J. Whelan, Nikolaus Grigorieff, Stephen C. Harrison

Open Access Articles

The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 A resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding ...


Lncrna Rp11-19e11 Is An E2f1 Target Required For Proliferation And Survival Of Basal Breast Cancer, A. Giro-Perafita, L. Luo, A. Khodadadi-Jamayran, M. Thompson, Betul Akgol-Oksuz, A. Tsirigos, B. D. Dynlacht, I. Sanchez, F. J. Esteva 2020 NYU Langone Health

Lncrna Rp11-19e11 Is An E2f1 Target Required For Proliferation And Survival Of Basal Breast Cancer, A. Giro-Perafita, L. Luo, A. Khodadadi-Jamayran, M. Thompson, Betul Akgol-Oksuz, A. Tsirigos, B. D. Dynlacht, I. Sanchez, F. J. Esteva

Open Access Articles

Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple-negative breast cancer), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas, we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs ...


Characterizing Patients With Recurrent Urinary Tract Infections In Vesicoureteral Reflux: A Pilot Study Of The Urinary Proteome, Dijana Vitko, Patricia Cho, Stephen A. Kostel, Shannon E. DiMartino, Lily D. Cabour, Matthew A. Migliozzi, Tanya Logvinenko, Peter G. Warren, John W. Froehlich, Richard S. Lee 2020 Boston Children's Hospital

Characterizing Patients With Recurrent Urinary Tract Infections In Vesicoureteral Reflux: A Pilot Study Of The Urinary Proteome, Dijana Vitko, Patricia Cho, Stephen A. Kostel, Shannon E. Dimartino, Lily D. Cabour, Matthew A. Migliozzi, Tanya Logvinenko, Peter G. Warren, John W. Froehlich, Richard S. Lee

Open Access Articles

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs ...


Determining The Antibacterial Activity And Mode Of Action Of Tirandamycin, Hailey Bouchard 2020 Claremont Colleges

Determining The Antibacterial Activity And Mode Of Action Of Tirandamycin, Hailey Bouchard

CMC Senior Theses

Tirandamycin is a small molecule natural product that has been isolated from various species of marine and terrestrial Streptomyces. The natural product has shown antibacterial activity against an array of Gram-positive and Gram-negative bacteria, showing promise as a pharmaceutical drug. Tirandamycin has 14 known derivatives, many of which have been created synthetically. Some of its derivatives are particularly potent against the high-risk bacteria vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Escherichia coli. However, the antibacterial potency of these derivatives has not been tested systematically leading to the possibility of discovering more potent derivatives of the drug which ...


Designing Peptides To Bind Kappa B Dna And Mimic Nf-Kappa B Protein Complexes, Nicholas A. Markowich 2020 Georgia Southern University

Designing Peptides To Bind Kappa B Dna And Mimic Nf-Kappa B Protein Complexes, Nicholas A. Markowich

University Honors Program Theses

Transcription factors are important proteins that regulate gene expression and protein synthesis. Transcription factors can either boost the gene’s transcription rate by helping RNA polymerase activate transcription or restrict it by interfering with RNA polymerase, thereby repressing transcription. Nuclear factor-kappa-B (NF-κB) transcription factors are a family of proteins that control the synthesis of proteins involved in many cellular processes such as inflammatory and immune responses, cell growth, and apoptosis. However, the overexpression and activation of these transcription factors is linked to deadly conditions such as cancer and neurodegenerative diseases which currently have few safe cures. The goal of this ...


The Structure Of The Endogenous Esx-3 Secretion System, Nicole Poweleit, Nadine Czudnochowski, Rachel Nakagawa, Donovan Trinidad, Kenan C. Murphy, Christopher M. Sassetti, Oren S. Rosenberg 2019 University of California, San Francisco

The Structure Of The Endogenous Esx-3 Secretion System, Nicole Poweleit, Nadine Czudnochowski, Rachel Nakagawa, Donovan Trinidad, Kenan C. Murphy, Christopher M. Sassetti, Oren S. Rosenberg

Open Access Articles

The ESX (or Type VII) secretion systems are protein export systems in mycobacteria and many Gram-positive bacteria that mediate a broad range of functions including virulence, conjugation, and metabolic regulation. These systems translocate folded dimers of WXG100-superfamily protein substrates across the cytoplasmic membrane. We report the cryo-electron microscopy structure of an ESX-3 system, purified using an epitope tag inserted with recombineering into the chromosome of the model organism Mycobacterium smegmatis. The structure reveals a stacked architecture that extends above and below the inner membrane of the bacterium. The ESX-3 protomer complex is assembled from a single copy of the EccB3 ...


Sensitive Detection Of Ebv Micrornas Across Cancer Spectrum Reveals Association With Decreased Survival In Adult Acute Myelocytic Leukemia, Mercedeh J. Movassagh, Cliff Oduor, Catherine Forconi, Ann M. Moormann, Jeffrey A. Bailey 2019 University of Massachusetts Medical School

Sensitive Detection Of Ebv Micrornas Across Cancer Spectrum Reveals Association With Decreased Survival In Adult Acute Myelocytic Leukemia, Mercedeh J. Movassagh, Cliff Oduor, Catherine Forconi, Ann M. Moormann, Jeffrey A. Bailey

Open Access Articles

Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association ...


Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom 2019 Chapman University

Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Glucocorticoids are widely used for the suppression of inflammation, but evidence is growing that they can have rapid, non-genomic actions that have been unappreciated. Diverse cell signaling effects have been reported for glucocorticoids, leading us to hypothesize that glucocorticoids alone can swiftly increase the 3′,5′-cyclic adenosine monophosphate (cAMP) production. We found that prednisone, fluticasone, budesonide, and progesterone each increased cAMP levels within 3 minutes without phosphodiesterase inhibitors by measuring real-time cAMP dynamics using the cAMP difference detector in situ assay in a variety of immortalized cell lines and primary human airway smooth muscle (HASM) cells. A membrane- impermeable ...


Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid 2019 Chapman University

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect ...


Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter 2019 University of Massachusetts Medical School

Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter

Open Access Articles

Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription ...


Agi-134: A Fully Synthetic Alpha-Gal Glycolipid That Converts Tumors Into In Situ Autologous Vaccines, Induces Anti-Tumor Immunity And Is Synergistic With An Anti-Pd-1 Antibody In Mouse Melanoma Models, Stephen M. Shaw, Kim Wigglesworth, Giles F. Whalen, Arik A. Zur 2019 Agalimmune Ltd.

Agi-134: A Fully Synthetic Alpha-Gal Glycolipid That Converts Tumors Into In Situ Autologous Vaccines, Induces Anti-Tumor Immunity And Is Synergistic With An Anti-Pd-1 Antibody In Mouse Melanoma Models, Stephen M. Shaw, Kim Wigglesworth, Giles F. Whalen, Arik A. Zur

Open Access Articles

Background: Treatments that generate T cell-mediated immunity to a patient's unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galalpha1-3Galbeta1-4GlcNAc (alpha-Gal) in situ leading to opsonization with pre-existing natural anti-alpha-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity.

Methods: Various immunological effects of coating tumor cells with alpha-Gal via AGI-134 in vitro ...


Functional Analysis Of Dnmt3a Dna Methyltransferase Mutations Reported In Patients With Acute Myeloid Leukemia, Daria A. Khrabrova, Andrei G. Loiko, Anastasia A. Tolkacheva, Natalia A. Cherepanova, Maria I. Zvereva, Olga V. Kirsanova, Elizaveta S. Gromova 2019 Lomonosov Moscow State University

Functional Analysis Of Dnmt3a Dna Methyltransferase Mutations Reported In Patients With Acute Myeloid Leukemia, Daria A. Khrabrova, Andrei G. Loiko, Anastasia A. Tolkacheva, Natalia A. Cherepanova, Maria I. Zvereva, Olga V. Kirsanova, Elizaveta S. Gromova

Open Access Articles

In mammals, DNA methylation is necessary for the maintenance of genomic stability, gene expression regulation, and other processes. During malignant diseases progression, changes in both DNA methylation patterns and DNA methyltransferase (MTase) genes are observed. Human de novo MTase DNMT3A is most frequently mutated in acute myeloid leukemia (AML) with a striking prevalence of R882H mutation, which has been extensively studied. Here, we investigate the functional role of the missense mutations (S714C, R635W, R736H, R771L, P777R, and F752V) found in the catalytic domain of DNMT3A in AML patients. These were accordingly mutated in the murine Dnmt3a catalytic domain (S124C, R45W ...


Identification Of The Hyaluronic Acid Pathway As A Therapeutic Target For Facioscapulohumeral Muscular Dystrophy, Alec M. DeSimone, John D. Leszyk, Kathryn Wagner, Charles P. Emerson, Jr. 2019 University of Massachusetts Medical School

Identification Of The Hyaluronic Acid Pathway As A Therapeutic Target For Facioscapulohumeral Muscular Dystrophy, Alec M. Desimone, John D. Leszyk, Kathryn Wagner, Charles P. Emerson, Jr.

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is linked to epigenetic derepression of the germline/embryonic transcription factor DUX4 in skeletal muscle. However, the etiology of muscle pathology is not fully understood, as DUX4 misexpression is not tightly correlated with disease severity. Using a DUX4-inducible cell model, we show that multiple DUX4-induced molecular pathologies that have been observed in patient-derived disease models are mediated by the signaling molecule hyaluronic acid (HA), which accumulates following DUX4 induction. These pathologies include formation of RNA granules, FUS aggregation, DNA damage, caspase activation, and cell death. We also observe previously unidentified pathologies including mislocalization of mitochondria and ...


Alanyl-Trna Synthetase Quality Control Prevents Global Dysregulation Of The Escherichia Coli Proteome, Paul Kelly, Nicholas Backes, Kyle Mohler, Christopher Buser, Arundhati Kavoor, Jesse Rinehart, Gregory Phillips, Michael Ibba 2019 The Ohio State University

Alanyl-Trna Synthetase Quality Control Prevents Global Dysregulation Of The Escherichia Coli Proteome, Paul Kelly, Nicholas Backes, Kyle Mohler, Christopher Buser, Arundhati Kavoor, Jesse Rinehart, Gregory Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mechanisms have evolved to prevent errors in replication, transcription, and translation of genetic material, with translational errors occurring most frequently. Errors in protein synthesis can occur at two steps, during tRNA aminoacylation and ribosome decoding. Recent advances in protein mass spectrometry have indicated that previous reports of translational errors have potentially underestimated the frequency of these events, but also that the majority of translational errors occur during ribosomal decoding, suggesting that aminoacylation errors are evolutionarily less tolerated. Despite that interpretation, there is evidence that some aminoacylation errors may be regulated, and thus provide a benefit to the cell, while others ...


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