A5071796341- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- HIV Research and Treatment
- RNA regulation and disease
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- CRISPR and Genetic Engineering
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- Cancer-related gene regulation
- Various Chemistry Research Topics
- Chemical Synthesis and Analysis
- Force Microscopy Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Molecular Biology Techniques and Applications
- Animal Disease Management and Epidemiology
- Microbial Natural Products and Biosynthesis
Stanford University
2015-2024
Resonance Research (United States)
2003-2015
Fairchild Semiconductor (United States)
1998-2005
MRC Laboratory of Molecular Biology
2003
University of Rochester
2003
SUNY Fredonia
2003
Scripps Research Institute
2001
University of California, Santa Cruz
1995-1998
Massachusetts Institute of Technology
1992-1994
Institut de Biologie Moléculaire et Cellulaire
1990-1993
Aminoglycoside antibiotics that bind to 30 S ribosomal A-site RNA cause misreading of the genetic code and inhibit translocation. The aminoglycoside antibiotic paromomycin binds specifically an oligonucleotide contains subunit A site, solution structure RNA-paromomycin complex was determined by nuclear magnetic resonance spectroscopy. in major groove model within a pocket created A-A base pair single bulged adenine. Specific interactions occur between chemical groups important for activity...
The messenger RNAs of human immunodeficiency virus-1 (HIV-1) have an RNA hairpin structure, TAR, at their 5′ ends that contains a six-nucleotide loop and three-nucleotide bulge. conformations TAR with arginine analog specifically bound the binding site for viral protein, Tat, were characterized by nuclear magnetic resonance (NMR) spectroscopy. Upon binding, bulge changes conformation, essential nucleotides U23 A27⋅U38, form base-triple interaction stabilizes hydrogen bonding to G26...
Using single-molecule fluorescence spectroscopy, time-resolved conformational changes between fluorescently labeled tRNA have been characterized within surface-immobilized ribosomes proceeding through a complete cycle of translation elongation. Fluorescence resonance energy transfer was used to observe aminoacyl-tRNA (aa-tRNA) stably accommodating into the aminoacyl site (A site) ribosome via multistep, elongation factor-Tu dependent process. Subsequently, molecules, bound at peptidyl and A...
At what point during translation do proteins fold? It is well established that can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside tunnel have so far detected only formation helical secondary structure and collapsed or partially structured intermediates. Here, using a combination cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer on single translating ribosomes, molecular dynamics simulations,...
Significance SARS-CoV-2 is the causative agent of COVID-19 pandemic. A molecular framework for how virus manipulates host cellular machinery to facilitate infection needed. Here, we integrate biochemical and single-molecule strategies reveal insight into NSP1 from inhibits translation initiation. directly binds small (40S) subunit human ribosome, which modulated by initiation factors. Further, mRNA compete with each other bind ribosome. Our findings suggest that presence on ribosomal...
Abstract Translation initiation is a major rate-limiting step for protein synthesis. However, recent studies strongly suggest that the efficiency of synthesis additionally regulated by multiple factors impact elongation phase. To assess influence early on synthesis, we employed library more than 250,000 reporters combined with in vitro and vivo expression assays. Here report identity amino acids encoded codons 3 to 5 yield. This effect independent tRNA abundance, translation efficiency, or...
The Tat protein of bovine immunodeficiency virus (BIV) binds to its target RNA, TAR, and activates transcription. A 14-amino acid arginine-rich peptide corresponding the RNA-binding domain BIV specifically biochemical in vivo experiments have identified amino acids nucleotides required for binding. solution structure RNA-peptide complex has now been determined by nuclear magnetic resonance spectroscopy. TAR forms a virtually continuous A-form helix with two unstacked bulged nucleotides....
A general method for large scale preparation of uniformly isotopically labeled ribonucleotides and RNAs is described. Bacteria are grown on isotopic growth medium, their nucleic acids harvested degraded to mononucleotides. These enzymatically converted into ribonucleoside triphosphates, which used in transcription reactions vitro prepare NMR studies. For 15N-labeling, E.coli 15N-ammonium sulfate, whereas 13C-labeling, Methylophilus methylotrophus 13C-methanol, more economical than...
Translational fidelity is established by ribosomal recognition of the codon-anticodon interaction within aminoacyl–transfer RNA (tRNA) site (A site) ribosome. Experiments are presented that reveal possible contacts between 16 S and complex. N1 methylation adenine at position 1492 (A1492) A1493 interfered with A-site tRNA binding. Mutation A1492 to guanine or cytosine also impaired The deleterious effects A1492G A1493G (or both) mutations were compensated 2′fluorine substitutions in mRNA...
The human immunodeficiency virus Tat protein binds specifically to an RNA stem-loop structure (TAR) that contains two helical stem regions separated by a three-nucleotide bulge. A single arginine within the basic region of mediates specific binding TAR, and as free amino acid also TAR. We have previously proposed model in which interaction guanidinium group with guanosine-26 (G26) pair phosphates is stabilized formation base triple between U23 bulge A27.U38 upper helix. Here we show NMR...