A5051136558- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Prion Diseases and Protein Misfolding
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- Insect Resistance and Genetics
- CRISPR and Genetic Engineering
- Polyoxometalates: Synthesis and Applications
- Cancer-related gene regulation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Endoplasmic Reticulum Stress and Disease
- Graph theory and applications
- Cell death mechanisms and regulation
- Genomics and Chromatin Dynamics
- Heat shock proteins research
- Cancer Treatment and Pharmacology
- Chemical Synthesis and Analysis
John Brown University
2024
Brown University
2014-2020
University of Toronto
2020
Hospital for Sick Children
2020
Providence College
2019
Article8 August 2017Open Access Transparent process Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity Zachary Monahan Department Pharmacology Molecular Therapeutics, Uniformed Services University, Bethesda, MD, USA Search for more papers by this author Veronica H Ryan Neuroscience Graduate Program, Brown Providence, RI, Abigail M Janke Pharmacology, Physiology, Biotechnology, Kathleen A Burke Shannon N Rhoads Gül Zerze Chemical Biomolecular...
Article9 February 2018Open Access Transparent process A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing Ailin Wang Department of Molecular Pharmacology, Physiology, Biotechnology, Brown University, Providence, RI, USA Search for more papers by this author Alexander E Conicella Graduate Program in Biology, Cell Biology Biochemistry, Hermann Broder Schmidt Stanford University School Medicine, Stanford, CA, Erik W Martin Structural St. Jude...
Liquid-liquid phase separation (LLPS) is involved in the formation of membraneless organelles (MLOs) associated with RNA processing. The RNA-binding protein TDP-43 present several MLOs, undergoes LLPS, and has been linked to pathogenesis amyotrophic lateral sclerosis (ALS). While some ALS-associated mutations disrupt self-interaction function, here we show that designed single can enhance assembly function via modulating helical structure. Using molecular simulation NMR spectroscopy, observe...
Article15 May 2018Open Access Source DataTransparent process Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics amyotrophic lateral sclerosis Pietro Fratta Corresponding Author [email protected] orcid.org/0000-0002-8762-8188 UCL Institute Neurology, MRC Centre for Neuromuscular Disease, London, UK Search more papers by this author Prasanth Sivakumar Jack Humphrey Genetics Institute, Kitty Lo Thomas Ricketts Mammalian Unit, Harwell, Hugo Oliveira Jose...
Many cancer-causing chromosomal translocations result in transactivating protein products encoding FET family (FUS, EWSR1, TAF15) low-complexity (LC) domains fused to a DNA binding domain from one of several transcription factors. Recent work demonstrates that higher-order assemblies LC bind the carboxy-terminal large subunit RNA polymerase II (RNA pol CTD), suggesting oncoproteins may mediate aberrant transcriptional activation by recruiting promoters target genes. Here we use nuclear...
Highlights•The GAF and CLAMP proteins have shared unique GA-rich binding sites•Variation within DNA recognition elements drives differential occupancy•CLAMP both promote MSL recruitment for X chromosome dosage compensationSummaryLittle is known about how variation in sequence composition alters transcription factor occupancy to precisely recruit large complexes. A key model understanding complexes are targeted the Drosophila compensation system which male-specific lethal (MSL) complex...
Abstract Despite decades of research, mechanisms by which co-transcriptional alternative splicing events are targeted to the correct genomic locations drive cell fate decisions remain unknown. By combining structural and molecular approaches, we define a new mechanism an essential transcription factor (TF) targets through physical functional interaction with RNA binding proteins (RBPs). We show that TF co-transcriptionally regulates sex-specific directly interacting subset target RNAs on...
Recent studies suggest that deposition of amyloid β (Aβ) into oligomeric aggregates and fibrils, hallmarks Alzheimer's disease, may be initiated by the aggregation Aβ species other than well-studied 40- 42-residue forms, Aβ40 Aβ42, respectively. Here we report on key structural, dynamic, kinetic parameters Aβ43, extended a single threonine at C-terminus relative to Aβ42. Using time course experiments, electron microscopy, combination nuclear magnetic resonance measurements including backbone...
Significance Maintaining a functional cell requires the collaboration of large number biomolecules that regulate key biochemical processes. The p97 protein is essential in this effort, interacting with adaptor molecules target it to different regions for specific functions. Here, we study structural dynamics complex formed between and p47 critical membrane assembly. Our data establish p47–p97 interaction partly regulated by are intrinsically disordered, manner depends on whether adenosine...
Abstract Liquid-liquid phase separation (LLPS) is involved in the formation of membraneless organelles (MLOs) associated with RNA processing. Present several MLOs, TDP-43 undergoes LLPS and linked to pathogenesis amyotrophic lateral sclerosis (ALS). While some disease variants disrupt self-interaction function, here we show that designed single mutations can enhance assembly function via modulating helical structure. Using molecular simulation NMR spectroscopy, observe large structural...