# overview
Understanding the mechanisms by which upstream open reading frames (uORFs) in mRNA transcripts control gene expression is currently the major focus of my laboratory. A substantial component of this work is focused on the uORF-encoded fungal arginine attenuator peptide (AAP). The major goal of this work is to understand the mechanism by which a nascent peptide encoded by this uORF controls the movement of ribosomes on mRNA and regulates gene expression. Control mechanisms mediated by uORFs and nascent peptides exist in mammals, fungi, plants, viruses, and bacteria, but relatively little is known of the molecular details of such control. The AAP is encoded by a uORF in the 5?-leader regions of mRNAs specifying the first enzyme in fungal arginine (Arg) biosynthesis. Synthesis of the AAP rapidly reduces gene expression in response to Arg. AAP-mediated regulation is observed in vivo in both Neurospora crassa and Saccharomyces cerevisiae and in vitro, using fungal, plant and animal extracts. The nascent AAP causes the ribosome to stall when the concentration of Arg is high.

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Single-Strand Specific DNA And RNA Endonucleases

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Endoplasmic Reticulum Stress (er Stress)

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
3404 Medicinal And Biomolecular Chemistry

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Endoplasmic Reticulum Stress (er Stress)

# keywords[]
3102 Bioinformatics And Computational Biology

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# keywords[]
Carbon-nitrogen Ligases With Glutamine As Amide-n-donor

# educationAndTraining[].organization.label
Massachusetts Institute of Technology - (Cambridge, Massachusetts, United States)

# educationAndTraining[].organization.label
Stanford University - (Stanford, California, United States)

# educationAndTraining[].organization.label
Cornell University - (Ithaca, New York, United States)

# publications[].label
Site-specific release of nascent chains from ribosomes at a sense codon.

# publications[].label
Reconstruction and validation of a genome-scale metabolic model for the filamentous fungus Neurospora crassa using FARM.

# publications[].label
The evolutionarily conserved eukaryotic arginine attenuator peptide regulates the movement of ribosomes that have translated it.

# publications[].label
Essential genes encoded by the mating-type locus of the human fungal pathogen Cryptococcus neoformans.

# publications[].label
Sequence requirements for ribosome stalling by the arginine attenuator peptide.

# publications[].label
Control of mRNA Stability in Fungi by NMD, EJC and CBC Factors Through 3'UTR Introns.

# publications[].label
The Neurospora Transcription Factor ADV-1 Transduces Light Signals and Temporal Information to Control Rhythmic Expression of Genes Involved in Cell Fusion.

# publications[].label
Synaptic vesicles isolated from the electric organ of Torpedo californica and from the central nervous system of Mus musculus contain small ribonucleic acids (sRNAs).

# publications[].label
The use of lacZ gene fusions in Neurospora crassa

# publications[].label
Structure of the Proteins and Genes for the Nuclear-Encoded Subunits of N. Crassa Cytochrome Oxidase

# publications[].label
Taxonomy and Halotolerance of Mesophilic Methanosarcina Strains, Assignment of Strains to Species, and Synonymy of Methanosarcina mazei and Methanosarcina frisia

# publications[].label
The Neurospora crassa genome: cosmid libraries sorted by chromosome.

# publications[].label
her-2 upstream open reading frame effects on the use of downstream initiation codons.

# publications[].label
Structure of the translating Neurospora ribosome arrested by cycloheximide.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA.

# publications[].label
Nuclear genes for cytochrome c oxidase subunits of Neurospora crassa. Isolation and characterization of cDNA clones for subunits IV, V, VI, and possibly VII.

# publications[].label
Transcriptional profiling of cross pathway control in Neurospora crassa and comparative analysis of the Gcn4 and CPC1 regulons.

# publications[].label
Early nonsense: mRNA decay solves a translational problem.

# publications[].label
The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum.

# publications[].label
Translation factor control of ribosome conformation during start codon selection.

# publications[].label
Circadian clock control of eIF2 phosphorylation is necessary for rhythmic translation initiation.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Evolutionary roles of upstream open reading frames in mediating gene regulation in fungi.

# publications[].label
Developmental expression of genes involved in conidiation and amino acid biosynthesis in Neurospora crassa.

# publications[].label
Dissection of a co-translational nascent chain separation event.

# publications[].label
A high-density single nucleotide polymorphism map for Neurospora crassa.

# publications[].label
Evolutionary changes in the fungal carbamoyl-phosphate synthetase small subunit gene and its associated upstream open reading frame.

# publications[].label
A recommendation for naming proteins in Neurospora

# publications[].label
A UV-induced mutation in neurospora that affects translational regulation in response to arginine.

# publications[].label
Posttranscriptional control of gene expression in filamentous fungi.

# publications[].label
Arginine changes the conformation of the arginine attenuator peptide relative to the ribosome tunnel.

# publications[].label
Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA).

# publications[].label
Ribosome stalling is responsible for arginine-specific translational attenuation in Neurospora crassa.

# publications[].label
Enabling a community to dissect an organism: overview of the Neurospora functional genomics project.

# publications[].label
Preparation of a Saccharomyces cerevisiae cell-free extract for in vitro translation.

# publications[].label
Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae.

# publications[].label
cpc-1, the general regulatory gene for genes of amino acid biosynthesis in Neurospora crassa, is differentially expressed during the asexual life cycle.

# publications[].label
Translational regulation in response to changes in amino acid availability in Neurospora crassa.

# publications[].label
Expression of herpes virus thymidine kinase in Neurospora crassa.

# publications[].label
The cell free protein synthesis system from the model filamentous fungus Neurospora crassa.

# publications[].label
Physical evidence for distinct mechanisms of translational control by upstream open reading frames.

# publications[].label
Neurospora crassa supersuppressor mutants are amber codon-specific.

# publications[].label
Nascent polypeptide sequences that influence ribosome function.

# publications[].label
The arginine attenuator peptide interferes with the ribosome peptidyl transferase center.

# publications[].label
Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling.

# publications[].label
Ribosome occupancy of the yeast CPA1 upstream open reading frame termination codon modulates nonsense-mediated mRNA decay.

# publications[].label
Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Non-optimal codon usage affects expression, structure and function of clock protein FRQ.

# publications[].label
A precise size-estimate for the small RNA products arising from Neurospora crassa Dicer activity

# publications[].label
The Neurospora crassa arg-2 locus. Structure and expression of the gene encoding the small subunit of arginine-specific carbamoyl phosphate synthetase.

# publications[].label
Role of an upstream open reading frame in mediating arginine-specific translational control in Neurospora crassa.

# publications[].label
Draft de novo transcriptome assembly and proteome characterization of the electric lobe of Tetronarce californica: a molecular tool for the study of cholinergic neurotransmission in the electric organ.

# publications[].label
Toeprint analysis of the positioning of translation apparatus components at initiation and termination codons of fungal mRNAs.

# publications[].label
Ribosome Reinitiation Directs Gene-specific Translation and Regulates the Integrated Stress Response.

# publications[].label
A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules.

# publications[].label
The Antidepressant Sertraline Induces the Formation of Supersized Lipid Droplets in the Human Pathogen Cryptococcus neoformans.

# publications[].label
Evolutionarily conserved features of the arginine attenuator peptide provide the necessary requirements for its function in translational regulation.

# publications[].label
Crucial elements that maintain the interactions between the regulatory TnaC peptide and the ribosome exit tunnel responsible for Trp inhibition of ribosome function.

# publications[].label
Genome-wide characterization of light-regulated genes in Neurospora crassa.

# publications[].label
General and Cross-Pathway Controls of Amino Acid Biosynthesis

# publications[].label
Synthesis of Differentially Halogenated Lissoclimide Analogues To Probe Ribosome E-Site Binding.

# publications[].label
The antidepressant drug sertraline is a novel inhibitor of yeast Pah1 and human lipin 1 phosphatidic acid phosphatases.

# publications[].label
Downstream control of upstream open reading frames.

# publications[].label
Developmental and photoregulation of three Neurospora crassa carotenogenic genes during conidiation induced by desiccation.

# publications[].label
Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding.

# publications[].label
Arginine-specific regulation mediated by the Neurospora crassa arg-2 upstream open reading frame in a homologous, cell-free in vitro translation system.

# publications[].label
Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5.

# publications[].label
Interactions of the TnaC nascent peptide with rRNA in the exit tunnel enable the ribosome to respond to free tryptophan.

# publications[].label
Conserved Upstream Open Reading Frame Nascent Peptides That Control Translation.

# publications[].label
Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1).

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
eRF1 mediates codon usage effects on mRNA translation efficiency through premature termination at rare codons.

# publications[].label
Developmental and Photoregulation of Three Neurospora crassa Carotenogenic Genes during Conidiation Induced by Desiccation.

# publications[].label
A nascent polypeptide domain that can regulate translation elongation.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response.

# publications[].label
The Stringency of Start Codon Selection in the Filamentous Fungus Neurospora crassa *

# publications[].label
Evolutionarily Conserved Features of the Arginine Attenuator Peptide Provide the Necessary Requirements for Its Function in Translational Regulation*

# publications[].label
Guidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR).

# publications[].label
The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections.

# publications[].label
Recommendations for assigning symbols and names to Neurospora crassa genes now that its genome has been sequenced.

# publications[].label
Characterization of chromosome ends in the filamentous fungus Neurospora crassa.

# publications[].label
A highly conserved mechanism of regulated ribosome stalling mediated by fungal arginine attenuator peptides that appears independent of the charging status of arginyl-tRNAs.

# publications[].label
Partial gene sequences for the A subunit of methyl-coenzyme M reductase (mcrI) as a phylogenetic tool for the family Methanosarcinaceae.

# publications[].label
Cytochrome oxidase subunit V gene of Neurospora crassa: DNA sequences, chromosomal mapping, and evidence that the cya-4 locus specifies the structural gene for subunit V.

# publications[].publisher
American Association for the Advancement of Science (AAAS)

# publications[].label
Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling

# publications[].label
The use of fungal in vitro systems for studying translational regulation.

# publications[].label
Regulatory protein that inhibits both synthesis and use of the target protein controls flagellar phase variation in Salmonella enterica.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
The genome sequence of the filamentous fungus Neurospora crassa.

# publications[].label
Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity.

# publications[].label
Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism.

# publications[].label
Circadian Clock-Controlled Translation of Specific Neurospora crassamRNAs Requires Rhythmic eIF2 Activity and P-Bodies

# publications[].label
E-site drug specificity of the human pathogen Candida albicans ribosome.

# publications[].publisher
American Association for the Advancement of Science (AAAS)

# publications[].label
Redundancy of the two dicer genes in transgene-induced posttranscriptional gene silencing in Neurospora crassa.

# researcherOn[].label
Determining Genetic Signatures of the Cryptococcal Response to Zoloft by an Integrated Approach Combining Transcriptome, Translatome and Genetic Screens

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Allergy and Infectious Diseases

# researcherOn[].label
Systems Biology of the Circadian Clock Output Network

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# streetAddress
Texas A&M University; Biology; 3258 TAMU