Medicine and Health Sciences Commons^™

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Clinical Pathway Using Arabic Written Medical Information To Improve Incontinence Healthcare Utilization, John F. Knapp, Codrut Radoiu, Emma Ross, Jack Vercnocke Md, Aron Liaw Md, Nivedita Dhar

Medical Student Research Symposium

Introduction and Objective: Metro Detroit holds ~13% of all Arabic speakers in the U.S.A. and 91% of those in Michigan. Evidence supports that patients who do not speak the local language have poor access to healthcare. This study describes our preliminary experience of managing Arabic only speaking women with bothersome stress urinary incontinence (SUI) from May 2022 to October 2023. These women routinely request same-sex interpreters, which is not always possible, leading to a lack of detailed translation. A potential solution is to use Arabic written medical information (AWMI). The purpose of the study was to retrospectively look at the …

Crispr-Cas9-Based Functional Interrogation Of Unconventional Translatome Reveals Human Cancer Dependency On Cryptic Non-Canonical Open Reading Frames, Caishang Zheng, Yanjun Wei, Peng Zhang, Kangyu Lin, Dandan He, Hongqi Teng, Ganiraju Manyam, Zhao Zhang, Wen Liu, Hye Rin Lindsay Lee, Ximing Tang, Wei He, Nelufa Islam, Antrix Jain, Yulun Chiu, Shaolong Cao, Yarui Diao, Sherita Meyer-Gauen, Magnus Höök, Anna Malovannaya, Wenbo Li, Ming Hu, Wenyi Wang, Han Xu, Scott Kopetz, Yiwen Chen

Student and Faculty Publications

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a …

The Pros Of Changing Trna Identity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.

Structure-Based Regulatory Role For The 5'Utr Of Rcnmv Rna2, Jennifer S H Im, Jasmine R Sheppard, K Andrew White

Student and Faculty Publications

Red clover necrotic mosaic virus (RCNMV) is a segmented positive-strand RNA virus consisting of RNA1 and RNA2. Previous studies demonstrated that efficient translation of RCNMV RNA2 requires de novo synthesis of RNA2 during infections, suggesting that RNA2 replication is required for its translation. We explored a potential mechanism underlying the regulation of replication-associated translation of RNA2 by examining RNA elements in its 5' untranslated region (5'UTR). Structural analysis of the 5'UTR suggested that it can form two mutually exclusive configurations: a more thermodynamically stable conformation, termed the 5'-basal stem structure (5'BS), in which 5'-terminal sequences are base paired, and an …

Improving Translatability Of Spinal Cord Injury Research By Including Age As A Demographic Variable, Andrew N. Stewart, Linda A. T. Jones, John C. Gensel

Department of Physical Therapy Faculty Papers

Pre-clinical and clinical spinal cord injury (SCI) studies differ in study design, particularly in the demographic characteristics of the chosen population. In clinical study design, criteria such as such as motor scores, neurological level, and severity of injury are often key determinants for participant inclusion. Further, demographic variables in clinical trials often include individuals from a wide age range and typically include both sexes, albeit historically most cases of SCI occur in males. In contrast, pre-clinical SCI models predominately utilize young adult rodents and typically use only females. While it is often not feasible to power SCI clinical trials to …

Ribosomal Rack1 Regulates The Dendritic Arborization By Repressing Fmrp Activity, Nicla Romano, Bruna Di Giacomo, Veronica Nobile, Antonella Borreca, Daniela Willems, Francesca Tilesi, Elisabetta Catalani, Manasi Agrawal, Kristy Welshhans, Sara Ricciardi, Davide Cervia, Marcello Ceci

Faculty Publications

FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational machinery to regulate the translation of its mRNA targets is not yet fully understood. Here, we show that FMRP localizes on translational machinery by interacting with the ribosomal binding protein, Receptor for Activated C Kinase 1 (RACK1). The binding of FMRP to RACK1 removes the translational repressive activity of FMRP and promotes the translation of PSD-95 mRNA, …

Mechanisms Of Mir-3189-3p-Mediated Inhibition Of C-Myc Translation In Triple Negative Breast Cancer, Cecilia Vittori, Duane Jeansonne, Hassan Yousefi, Celeste Faia, Zhen Lin, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

Background: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of estrogen receptor, progesterone receptor, and HER2. Our lab previously characterized miR-3189-3p as a microRNA with potent anti-cancer activity against glioblastoma. Here, we hypothesized a similar activity in TNBC cells. As miR-3189-3p is predicted to target a variety of RNA binding proteins, we further hypothesized an inhibitory effect of this miRNA on protein synthesis. Methods: MDA-MB-231 and MDA-MB-468 cells were used to investigate the effect of miR-3189-3p on cell proliferation, migration, and invasion. TGCA database was used to analyze the expression of miR-3189-3p, …

Validation Of A Brazilian Portuguese Measure Of Family Resources In A Sample Of Parents To Children With Congenital Zika Virus Syndrome, Sarah Barker Ladd

College of Education and Human Sciences: Dissertations, Theses, and Student Research

In the aftermath of the 2015 Zika virus outbreak in Brazil, thousands of children and their families continue to face challenges associated with Congenital Zika Syndrome, a developmental condition associated with microcephaly and other serious birth defects affecting the central nervous system. Family-centered rehabilitative care is critical to optimize the trajectories of children who have significant developmental disabilities like CZS. These services involve assessing for the presence of family resources that may help to promote positive outcomes for children. Little is known regarding family resources in the context of caring for a child with CZS in Brazil due to the …

Deacylated Trna Accumulation Is A Trigger For Bacterial Antibiotic Persistence Independent Of The Stringent Response, Whitney N. Wood, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence occurs when bacteria are treated with an antibiotic and the majority of the population rapidly dies off, but a small subpopulation enters into a dormant, persistent state and evades death. Diverse pathways leading to nucleoside triphosphate (NTP) depletion and restricted translation have been implicated in persistence, suggesting alternative redundant routes may exist to initiate persister formation. To investigate the molecular mechanism of one such pathway, functional variants of an essential component of translation (phenylalanyltRNA synthetase [PheRS]) were used to study the effects of quality control on antibiotic persistence. Upon amino acid limitation, elevated PheRS quality control led …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

New Frontiers In Translational Research: Touchscreens, Open Science, And The Mouse Translational Research Accelerator Platform, Jacqueline A. Sullivan, Julie R. Dumont, Sara Memar, Miguel Skirzewski, Jinxia Wan, Maryam H. Mofrad, Hassam Zafar Ansari, Yulong Li, Lyle Muller, Vania F. Prado, Marco A.M. Prado, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2020 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high-level cognitive functions including memory, attention, motivation, and decision-making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state-of-the-art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is …

Cross-Cultural Adaptions And Measurement Properties Of The Worc (Western Ontario Rotator Cuff Index): A Systematic Review, R Furtado, Jc Macdermid, G Nazari, Dm Bryant

Bone and Joint Institute

Background To evaluate the translations, cross-cultural adaptation procedures and measurement properties of the Western Ontario Rotator Cuff Index (WORC), when it is adapted for different cultures. Methods A systematic review was performed, considering different cultural adaptions of the WORC accessible through MEDLINE, CINAHL, EMBASE and/or Google Scholar. Included were prospective cohort studies that used an adapted version of the WORC to measure QoL in patients with rotator cuff disorders. All studies were evaluated according to the current guidelines for cross-cultural adaptations and measurement properties. Results The search retrieved 14 studies that met the inclusion criteria. According to the recommended guidelines …

Considering Augmentative And Alternative Communication Research For Brain-Computer Interface Practice, Kevin M. Pitt, Jonathan S. Brumberg, Adrienne R. Pitt

Department of Special Education and Communication Disorders: Faculty Publications

Purpose: Brain-computer interfaces (BCIs) aim to provide access to augmentative and alternative communication (AAC) devices via brain activity alone. However, while BCI technology is expanding in the laboratory setting, there is minimal incorporation into clinical practice. Building upon established AAC research and clinical best practices may aid the clinical translation of BCI practice, allowing advancements in both fields to be fully leveraged.

Method: A multidisciplinary team developed considerations for how BCI products, practice, and policy may build upon existing AAC research, based upon published reports of existing AAC and BCI procedures.

Outcomes/Benefits: Within each consideration, a review of BCI research …

Annual Research Review: Educational Neuroscience: Progress And Prospects, Michael S.C. Thomas, Daniel Ansari, Victoria C.P. Knowland

Brain and Mind Institute Researchers' Publications

© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health. Educational neuroscience is an interdisciplinary research field that seeks to translate research findings on neural mechanisms of learning to educational practice and policy and to understand the effects of education on the brain. Neuroscience and education can interact directly, by virtue of considering the brain as a biological organ that needs to be in the optimal condition to learn (‘brain health’); or indirectly, as neuroscience shapes psychological theory and psychology influences education. In …

Controlled Ecological Evaluation Of An Implemented Exercise Training Programme To Prevent Lower Limb Injuries In Sport: Differences In Implementation Activity, Alex Donaldson, Belinda J. Gabbe, David G. Lloyd, Jill Cook, Caroline F. Finch

Research outputs 2014 to 2021

OBJECTIVE: The public health benefits of injury prevention programmes are maximised when programmes are widely adopted and adhered to. Therefore, these programmes require appropriate implementation support. This study evaluated implementation activity outcomes associated with the implementation of FootyFirst, an exercise training injury prevention programme for community Australian football, both with (FootyFirst+S) and without (FootyFirst+NS) implementation support. METHOD: An evaluation plan based on the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) Sports Setting Matrix was applied in a controlled ecological evaluation of the implementation of FootyFirst. RE-AIM dimension-specific (range: 0-2) and total RE-AIM scores (range: 0-10) were derived by triangulating data from …

Concise Review: Stem Cell Therapy For Stroke Patients: Are We There Yet?, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Four decades of preclinical research demonstrating survival, functional integration, and behavioral effects of transplanted stem cells in experimental stroke models have provided ample scientific basis for initiating limited clinical trials of stem cell therapy in stroke patients. Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as …

Global Phosphoproteomics Of Ccr5-Tropic Hiv-1 Signaling Reveals Reprogramming Of Cellular Protein Production Pathways And Identifies P70-S6k1 And Mk2 As Hiv-Responsive Kinases Required For Optimal Infection Of Cd4+ T Cells, Danica D. Wiredja, Caroline O. Tabler, Daniela M. Schlatzer, Ming Li, Mark R. Chance, John C. Tilton

Faculty Scholarship

Background: Viral reprogramming of host cells enhances replication and is initiated by viral interaction with the cell surface. Upon human immunodeficiency virus (HIV) binding to CD4+ T cells, a signal transduction cascade is initiated that reorganizes the actin cytoskeleton, activates transcription factors, and alters mRNA splicing pathways. Methods: We used a quantitative mass spectrometry-based phosphoproteomic approach to investigate signal transduction cascades initiated by CCR5-tropic HIV, which accounts for virtually all transmitted viruses and the vast majority of viruses worldwide. Results: CCR5-HIV signaling induced significant reprogramming of the actin cytoskeleton and mRNA splicing pathways, as previously described. In addition, CCR5-HIV signaling …

Exclusion Criteria And Generalizability In Bipolar Disorder Treatment Trials, Jessie J. Wong, Nev Jones, Christine Timko, Keith Humphreys

Mental Health Law & Policy Faculty Publications

Objective: The current paper reviews the English-language research on exclusion criteria in bipolar disorder treatment trials and discusses how study samples compare to the general bipolar patient population.

Methods: & Results: Across 8 identified studies of exclusion criteria and their impact, between 55% and 96% of people with bipolar disorder would be excluded from treatment research. The number of exclusion criteria varies across bipolar disorder treatment research, with one study estimate of a median of 7 criteria used across studies. The criteria that excluded the greatest number of potential participants were comorbid substance use disorder, suicidal risk, and comorbid medical …

Patient Perspectives On Improving Osteoarthritis Management In Urban And Rural Communities, Shabana Amanda Ali, Kathleen Ellen Walsh, Marita Kloseck

Bone and Joint Institute

© 2018 Ali et al. Introduction: Although there is no cure for osteoarthritis (OA), there are lifestyle modifications that can mitigate symptoms such as pain, and improve management of the disease. This information is not always translated to community-dwelling seniors. Individuals in rural areas often face additional challenges due to geographic isolation and decreased access to community services. Methods: We used qualitative research methodology (hermeneutic phenomenology) to better understand the lived experiences of urban and rural community-dwelling seniors diagnosed with OA. We explored their sources of information about OA, how they manage their OA pain, and how OA management could …

Evaluating The Impact Of A Falls Prevention Community Of Practice In A Residential Aged Care Setting: A Realist Approach, J Francis-Coad, C Etherton-Beer, C Bulsara, N Blackburn, P Chivers, A Hill

Physiotherapy Papers and Journal Articles

Background: Falls are a major socio-economic problem among residential aged care (RAC) populations resulting in high rates of injury including hip fracture. Guidelines recommend that multifactorial prevention strategies are implemented but these require translation into clinical practice. A community of practice (CoP) was selected as a suitable model to support translation of the best available evidence into practice, as it could bring together likeminded people with falls expertise and local clinical knowledge providing a social learning opportunity in the pursuit of a common goal; falls prevention. The aims of this study were to evaluate the impact of a falls prevention …

Structural Basis For Earp-Mediated Arginine Glycosylation Of Translation Elongation Factor Ef-P, Ralph Krafczyk, Jakub Macošek, Pravin Kumar Ankush Jagtap, Daniel Gast, Swetlana Wunder, Prithiba Mitra, Amit Kumar Jha, Jürgen Rohr, Anja Hoffmann-Röder, Kirsten Jung, Janosch Hennig, Jürgen Lassak

Pharmaceutical Sciences Faculty Publications

Glycosylation is a universal strategy to posttranslationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline-specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida. The enzyme is composed of two opposing domains with Rossmann folds, thus constituting a B pattern-type glycosyltransferase (GT-B). While dTDP-β-L-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the KOW-like N-domain of EF-P. Based on our data, we propose a structural model for …

Carbonyl Reduction By Ymfi Completes The Modification Of Ef-P In Bacillus Subtilis To Prevent Accumulation Of An Inhibitory Modification State, Katherine R. Hummels, Anne Witzky, Andrei Rajkovic, Rodney Tollerson Ii, Lisa A. Jones, Michael Ibba, Daniel B. Kearns

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translation elongation factor P (EF‐P) in Bacillus subtilis is required for a form of surface migration called swarming motility. Furthermore, B. subtilis EF‐P is post‐translationally modified with a 5‐aminopentanol group but the pathway necessary for the synthesis and ligation of the modification is unknown. Here we determine that the protein YmfI catalyzes the reduction of EF‐P‐5 aminopentanone to EF‐P‐5 aminopentanol. In the absence of YmfI, accumulation of 5‐aminopentanonated EF‐P is inhibitory to swarming motility. Suppressor mutations that enhanced swarming in the absence of YmfI were found at two positions on EF‐P, including one that changed the conserved modification site (Lys …

Cultural Adaptation Of The Test Of Narrative Language (Tnl) Into Brazilian Portuguese, Natalia Freitas Rossi, Tâmara De Andrade Lindau, Ronald B. Gillam, Célia Maria Giacheti

Communicative Disorders and Deaf Education Faculty Publications

Purpose: To accomplish the translation and cultural adaptation of the Test of Narrative Language (TNL) into Brazilian Portuguese.

Methods: The TNL is a formal instrument which assesses narrative comprehension and oral narration of children between the ages of 5-0 and 11-11 (years-months). The TNL translation and adaptation process had the following steps: (1) translation into the target language; (2) summary of the translated versions; (3) back-translation; (4) checking of the conceptual, semantics and cultural equivalence process and (5) pilot study (56 children within the test age range and from both genders).

Results: The adapted version maintained the same structure as …

Translation Control Of Swarming Proficiency In Bacillus Subtilis By 5-Amino-Pentanolylated Elongation Factor P, Andrei Rajkovic, Katherine R. Hummels, Anne Witzky, Sarah Erickson, Philip R. Gafken, Julian P. Whitelegge, Kym F. Faull, Daniel B. Kearns, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys³² of B. subtilis EF-P that is …

Multiple Quality Control Pathways Limit Non-Protein Amino Acid Use By Yeast Cytoplasmic Phenylalanyl-Trna Synthetase, Adil Moghal, Lin Hwang, Kym F. Faull, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Non-protein amino acids, particularly isomers of the proteinogenic amino acids, present a threat to proteome integrity if they are mistakenly inserted into proteins. Quality control during aminoacyl-tRNA synthesis reduces non-protein amino acid incorporation by both substrate discrimination and proofreading. For example phenylalanyl-tRNA synthetase (PheRS) proofreads the non-protein hydroxylated phenylalanine derivative m-Tyr after its attachment to tRNA^Phe. We now show in Saccharomyces cerevisiae that PheRS misacylation of tRNA^Phe with the more abundant Phe oxidation product o-Tyr is limited by kinetic discrimination against o-Tyr-AMP in the transfer step followed by o-Tyr-AMP release from the synthetic …

Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads …

Raising Awareness Of Research Evidence Among Health Professionals Delivering Dementia Care: Are Knowledge Translation Workshops Useful?, Belinda J. Goodenough, Richard Fleming, Michael Young, Kim Burns, Cindy Jones, Fallon M. Forbes

Faculty of Science, Medicine and Health - Papers: part A

Providing information about the latest research via educational sessions to health professionals caring for people with dementia may be insufficient to drive change. This project explored self-reported impacts on practice change of adding information about knowledge translation (KT) to a national dementia education program. Six national workshop days were held. Each provided the option of participating in a Principles of KT and innovation implementation seminar in addition to a clinical topic update (sexualities and dementia, or managing behavioral and psychological symptoms of dementia). Six months postworkshop, 321 participants were invited to complete a research utilization survey. Seventy-five responded. KT seminar …

Mistranslation Of The Genetic Code, Adil Moghal, Kyle Mohler, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

During mRNA decoding at the ribosome, deviations from stringent codon identity, or “mistranslation,” are generally deleterious and infrequent. Observations of organisms that decode some codons ambiguously, and the discovery of a compensatory increase in mistranslation frequency to combat environmental stress have changed the way we view “errors” in decoding. Modern tools for the study of the frequency and phenotypic effects of mistranslation can provide quantitative and sensitive measurements of decoding errors that were previously inaccessible. Mistranslation with non‐protein amino acids, in particular, is an enticing prospect for new drug therapies and the study of molecular evolution.

Translation Initiation Rate Determines The Impact Of Ribosome Stalling On Bacterial Protein Synthesis, Steven J. Hersch, Sara Elgamal, Assaf Katz, Michael Ibba, William Wiley Navarre

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Ribosome stalling during translation can be caused by a number of characterized mechanisms. However, the impact of elongation stalls on protein levels is variable, and the reasons for this are often unclear. To investigate this relationship, we examined the bacterial translation elongation factor P (EF-P), which plays a critical role in rescuing ribosomes stalled at specific amino acid sequences including polyproline motifs. In previous proteomic analyses of both Salmonella and Escherichia coli efp mutants, it was evident that not all proteins containing a polyproline motif were dependent on EF-P for efficient expression in vivo . The α- and β-subunits of …