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Articles 1 - 13 of 13
Full-Text Articles in Molecular Biology
Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana
Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Glutamyl-tRNA (Glu-tRNAGlu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNAGlu can become scarce, resulting in competition between the two pathways for this aminoacyl-tRNA. In Acidithiobacillus ferrooxidans, glutamyl-tRNA synthetase 1 (GluRS1) is the main enzyme that synthesizes Glu-tRNAGlu. Previous studies have shown that GluRS1 is inactivated in vitro by hydrogen peroxide (H2O2). This raises the question as to whether H2O2 negatively affects …
Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs
Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs
Elizabeth J. Luna
X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence …
The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation, Kan Kobayashi, Assaf Katz, Andrei Rajkovic, Ryohei Ishii, Owen E. Branson, Michael A. Freitas, Ryuichiro Ishitani, Michael Ibba, Osamu Nureki
The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation, Kan Kobayashi, Assaf Katz, Andrei Rajkovic, Ryohei Ishii, Owen E. Branson, Michael A. Freitas, Ryuichiro Ishitani, Michael Ibba, Osamu Nureki
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
EF-P is a bacterial tRNA-mimic protein, which accelerates the ribosome-catalyzed polymerization of poly-prolines. In Escherichia coli, EF-P is post-translationally modified on a conserved lysine residue. The post-translational modification is performed in a two-step reaction involving the addition of a β-lysine moiety and the subsequent hydroxylation, catalyzed by PoxA and YfcM, respectively. The β-lysine moiety was previously shown to enhance the rate of poly-proline synthesis, but the role of the hydroxylation is poorly understood. We solved the crystal structure of YfcM and performed functional analyses to determine the hydroxylation mechanism. In addition, YfcM appears to be structurally distinct from any …
Mistranslation Of The Genetic Code, Adil Moghal, Kyle Mohler, Michael Ibba
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.
Relaxed Substrate Specificity Leads To Extensive Trna Mischarging By Streptococcus Pneumoniae Class I And Class Ii Aminoacyl-Trna Synthetases, Jennifer Shepherd, Michael Ibba
Relaxed Substrate Specificity Leads To Extensive Trna Mischarging By Streptococcus Pneumoniae Class I And Class Ii Aminoacyl-Trna Synthetases, Jennifer Shepherd, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases provide the first step in protein synthesis quality control by discriminating cognate from noncognate amino acid and tRNA substrates. While substrate specificity is enhanced in many instances by cis- and trans-editing pathways, it has been revealed that in organisms such as Streptococcus pneumoniae some aminoacyl-tRNA synthetases display significant tRNA mischarging activity. To investigate the extent of tRNA mischarging in this pathogen, the aminoacylation profiles of class I isoleucyl-tRNA synthetase (IleRS) and class II lysyl-tRNA synthetase (LysRS) were determined. Pneumococcal IleRS mischarged tRNAIle with both Val, as demonstrated in other bacteria, and Leu in a tRNA sequence-dependent …
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
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 …
Ef-P Dependent Pauses Integrate Proximal And Distal Signals During Translation, Sara Elgamal, Assaf Katz, Steven J. Hersch, David Newsom, Peter White, William Wiley Navarre, Michael Ibba
Ef-P Dependent Pauses Integrate Proximal And Distal Signals During Translation, Sara Elgamal, Assaf Katz, Steven J. Hersch, David Newsom, Peter White, William Wiley Navarre, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is required for the efficient synthesis of proteins with stretches of consecutive prolines and other motifs that would otherwise lead to ribosome pausing. However, previous reports also demonstrated that levels of most diprolyl-containing proteins are not altered by the deletion of efp. To define the particular sequences that trigger ribosome stalling at diprolyl (PPX) motifs, we used ribosome profiling to monitor global ribosome occupancy in Escherichia coli strains lacking EF-P. Only 2.8% of PPX motifs caused significant ribosomal pausing in the Δefp strain, with up to a 45-fold increase in ribosome density observed at …
Trnas As Regulators Of Biological Processes, Medha Raina, Michael Ibba
Trnas As Regulators Of Biological Processes, Medha Raina, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Transfer RNAs (tRNA) are best known for their role as adaptors during translation of the genetic code. Beyond their canonical role during protein biosynthesis, tRNAs also perform additional functions in both prokaryotes and eukaryotes for example in regulating gene expression. Aminoacylated tRNAs have also been implicated as substrates for non-ribosomal peptide bond formation, post-translational protein labeling, modification of phospholipids in the cell membrane, and antibiotic biosyntheses. Most recently tRNA fragments, or tRFs, have also been recognized to play regulatory roles. Here, we examine in more detail some of the new functions emerging for tRNA in a variety of cellular processes …
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress …
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons, Medha Raina, Adil Moghal, Amanda Kano, Mathew Jerums, Paul D. Schnier, Shun Luo, Rohini Deshpande, Pavel D. Bondarenko, Henry Lin, Michael Ibba
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons, Medha Raina, Adil Moghal, Amanda Kano, Mathew Jerums, Paul D. Schnier, Shun Luo, Rohini Deshpande, Pavel D. Bondarenko, Henry Lin, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, …
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
An ABC protein that binds the ribosomal exit site suggests a new mechanism for direct regulation of translation in response to changing ATP levels in the cell.
Ecdysis Triggering Hormone And Its Role In Juvenile Hormone Synthesis In The Yellow-Fever Mosquito, Aedes Aegypti, Maria Areiza
Ecdysis Triggering Hormone And Its Role In Juvenile Hormone Synthesis In The Yellow-Fever Mosquito, Aedes Aegypti, Maria Areiza
FIU Electronic Theses and Dissertations
Ecdysis triggering hormone (ETH) is a neuropeptide known for its role in the orchestration of ecdysis. However, its role in the regulation of Juvenile Hormone (JH) synthesis is unknown. In Aedes aegypti, JH is synthesized by the corpora allata (CA) and titers are tightly regulated by allatoregulatory factors. In this study I describe the effect of ETH on JH synthesis during the late pupal stage and in the adult female after blood feeding. Analysis of ETH receptor (ETHRs) expression showed that ETHRs are present in both the CA and the corpora cardiaca (CC), a neurohemal organ. The data suggest …
Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper
Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper
Medical Diagnostics & Translational Sciences Faculty Publications
Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …