A5054004495- Autophagy in Disease and Therapy
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Mitochondrial Function and Pathology
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Oral microbiology and periodontitis research
- Nuclear Engineering Thermal-Hydraulics
- Impact of Technology on Adolescents
- Genomics and Rare Diseases
- Signaling Pathways in Disease
- Lipid metabolism and biosynthesis
- Chromium effects and bioremediation
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Viral-associated cancers and disorders
- Fungal and yeast genetics research
- Toxoplasma gondii Research Studies
- Advanced Electron Microscopy Techniques and Applications
- Cancer, Hypoxia, and Metabolism
Dartmouth College
2020-2025
Dartmouth Psychiatric Research Center
2023-2024
Dartmouth Cancer Center
2023-2024
Harvard University
2015-2019
Pennsylvania State University
2018
Harvard University Press
2015
Howard Hughes Medical Institute
2009-2013
Johns Hopkins University
2009-2013
Johns Hopkins Medicine
2009
Miami University
2006-2007
No-go decay (NGD) is one of several messenger RNA (mRNA) surveillance systems dedicated to the removal defective mRNAs from available pool. Two interacting factors, Dom34 and Hbs1, are genetically implicated in NGD yeast. Using a reconstituted yeast translation system, we show that Dom34:Hbs1 interacts with ribosome promote subunit dissociation peptidyl-tRNA drop-off. Our data further indicate these recycling activities shared by homologous termination factor complex eRF1:eRF3, suggesting...
Although well defined in bacterial systems, the molecular mechanisms underlying ribosome recycling eukaryotic cells have only begun to be explored. Recent studies proposed a direct role for termination factors eRF1 and eRF3 (and related Dom34 Hbs1) downstream processes; however, our understanding of connection between eukaryotes is limited. Here, using an vitro reconstituted yeast translation system, we identify key multifunctional ABC-family protein Rli1 stimulating both eRF1-mediated...
The power of forward genetics in yeast is the foundation on which field autophagy research firmly stands. Complementary work higher eukaryotes has revealed both deep conservation this process, as well novel mechanisms by regulated context development, immunity, and neuronal homeostasis. recent emergence new clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based technologies begun facilitating efforts to define factors pathways genetic screening...
Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling vitro. Here, we uncover roles for HCR1 eIF3 translation vivo. A substantial proportion of eIF3, release factor 3 (eRF3) but not eIF5 (a well-defined “initiation-specific” binding partner eIF3) specifically co-sediments with 80S couples isolated from RNase-treated heavy polysomes an eRF1-dependent manner, indicating...
Article23 November 2020Open Access Source DataTransparent process Receptor-mediated clustering of FIP200 bypasses the role LC3 lipidation in autophagy Amelia E Ohnstad Department Biochemistry and Cell Biology, Geisel School Medicine at Dartmouth, Hanover, NH, USA Search for more papers by this author Jose M Delgado Brian J North Isha Nasa orcid.org/0000-0001-7699-795X Norris Cotton Cancer Center, Lebanon, Arminja N Kettenbach orcid.org/0000-0003-3979-4576 Sebastian W Schultz Centre...
Eukaryotic mRNAs are subject to quality control mechanisms that degrade defective mRNAs. In yeast, with stalls in translation elongation targeted for endonucleolytic cleavage by No-Go decay (NGD). The triggered is dependent on Dom34p and Hbs1p, Dom34 has been proposed be the endonuclease responsible mRNA cleavage. We created several mutants examined their effects NGD yeast. identified mutations loops of structure affect NGD. contrast, inactivating nuclease domain do not vivo. Moreover, we...
Nuclear lamin filaments and associated proteins form a nucleoskeletal ("lamina") network required for transcription, replication, chromatin organization epigenetic regulation in metazoans. Lamina defects cause human disease ("laminopathies") are linked to aging. Barrier-to-autointegration factor (BAF) is mobile essential component of the nuclear lamina that binds directly histones, lamins LEM-domain proteins, including inner membrane protein emerin, has roles structure, mitosis gene...
Mitophagy is a cellular process that enables the selective degradation of damaged, dysfunctional, or superfluous mitochondria. During mitophagy, specific proteins recognize and tag mitochondria for degradation. These tagged are engulfed by specialized structures called phagophores then mature into autophagosomes/mitophagosomes. Mitophagosomes subsequently transport their mitochondrial cargo to lysosomes, where broken down recycled. While PINK1-PRKN-dependent mitophagy pathway well...
During autophagy, toxic cargo is encapsulated by autophagosomes and trafficked to lysosomes for degradation. NBR1, an autophagy receptor targeting ubiquitinated aggregates, serves as a model studying the multivalent, heterotypic interactions of cargo-bound receptors. Here, we find that three critical NBR1 partners—ATG8-family proteins, FIP200, TAX1BP1—each bind distinct, overlapping determinants within short linear interaction motif (SLiM). To explore whether SLiMs extend beyond analyzed...
MicroRNAs (miRNAs) are an abundant class of ∼22 nucleotide (nt) long noncoding RNAs that negatively regulate gene expression post-transcriptionally through imperfect base-pairing interactions with sequences in the target messenger RNA (mRNA). We examined bantam miRNA 3′ untranslated region (UTR) hid mRNA, and a synthetic derivative, Drosophila S2 cells order to define relative contributions proposed binding sites. The contribution repression reporter constructs carrying different UTRs was...
During autophagy, potentially toxic cargo is enveloped by a newly formed autophagosome and trafficked to the lysosome for degradation. Ubiquitinated protein aggregates, key target are identified multiple autophagy receptors. NBR1 an archetypal receptor excellent model deciphering role of multivalent, heterotypic interactions made cargo-bound Using as model, we find that three critical binding partners - ATG8-family proteins, FIP200, TAX1BP1 each bind short linear interaction motif (SLiM)...
Actinobacillus actinomycetemcomitans, a pathogen associated with oral and extra-oral infections, requires iron to grow under limiting conditions. Although incapable of producing siderophores, this could acquire by direct interaction compounds such as haemin, haemoglobin, lactoferrin transferrin. In work the ability different A. actinomycetemcomitans strains bind use sources was tested. None tested used or transferrin sole iron. However, all them FeCl(3) haemin chelated Dot-blot binding...
Summary Selective autophagy comprises cytoplasm-to-lysosome trafficking routes that transport cargos using double-membrane vesicles (autophagosomes). Cargos are detected by receptor proteins, which typically also bind to lipid-conjugated LC3 proteins on autophagosome membranes. We dissected lysosomal delivery of four SQSTM1-like receptors genome-wide CRISPR screening looking for novel autophagy-related (ATG) factors and routes. uncovered new mammalian ATG including TMEM41B, an endoplasmic...
Selective macroautophagy (hereafter autophagy) can eliminate large cytotoxic structures that are designated for degradation by autophagy receptors. In our recent paper, we showed a key function of target-bound receptors is to activate the kinase, Atg1, via interactions with scaffold protein Atg11. Our work thus reveals mechanism which target recognition coordinates earliest steps in autophagosome biogenesis.