- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- RNA regulation and disease
- Viral Infections and Immunology Research
- interferon and immune responses
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Fungal and yeast genetics research
- Viral gastroenteritis research and epidemiology
- Genomics and Phylogenetic Studies
- Skin and Cellular Biology Research
- Nuclear Structure and Function
- Cytokine Signaling Pathways and Interactions
- Telomeres, Telomerase, and Senescence
- Ubiquitin and proteasome pathways
National Cancer Institute
2025
Center for Cancer Research
2017-2023
National Cancer Institute
2015-2023
National Institutes of Health
2015-2023
Yale University
2010-2019
Yale Cancer Center
2015-2016
University of New Haven
2013
Howard Hughes Medical Institute
1997-2006
University Hospitals of Cleveland
1999
Case Western Reserve University
1999
Small ribonucleic acid (RNA)-protein complexes precipitated by anti-Ro and anti-La antibodies from lupus patients have been examined with emphasis on their RNA components. In both ribonucleoprotein (RNP) classes, the numbers of different molecules sequences vary between mouse human cells. The complex mixtures La RNAs include two previously sequenced 4.5S cells 5S ribosomal RNA-like All Ro possess 5-triphosphates. Some internal modifications typical transfer RNAs. RNPs are quite stable...
Patients with systemic lupus erythematosus and other rheumatic diseases often possess autoantibodies directed against discrete classes of small ribonucleoprotein particles (RNPs). The class recognized by anti-Ro antibodies contains from two to four cytoplasmic RNAs, depending on the mammalian species examined. We find that an antigenic polypeptide 60 kDa is major protein residing in Ro RNPs human HeLa cells. To determine what common feature RNA sequence or structure protein, we carried out...
Commensal bacterial orthologs of the human autoantigen Ro60 may trigger cross-reactive T and B cells that initiate sustain chronic autoimmunity in lupus.
Although the La autoantigen binds to 3' ends of all nascent polymerase III transcripts, its function in vivo has long been unclear. S. cerevisiae cells lacking protein homolog Lhp1p are viable, containing a mutation that disrupts anticodon stem tRNA(Ser)CGA require for growth. We demonstrate wild-type pre-tRNA(Ser)CGA and other pre-tRNAs, is required normal endonucleolytic removal trailer sequence. In Lhp1p, removed by exonuclease(s). maturation mutant requires introduction second restores...
The Ro autoantigen is a 60-kD protein that usually found in small cytoplasmic RNA-protein complexes known as RNPs. Although the RNPs are abundant and conserved components of variety vertebrate invertebrate cells, their function unknown. We have discovered also complexed with certain variant 5S rRNAs Xenopus oocytes. These RNAs contain one or more point mutations compared major oocyte rRNA sequence well additional nucleotides at 3' end. demonstrate binds specifically mutant containing...
Small ribonucleic acid (RNA)-protein complexes precipitated by anti-Ro and anti-La antibodies from lupus patients have been examined with emphasis on their RNA components. In both ribonucleoprotein (RNP) classes, the numbers of different molecules sequences vary between mouse human cells. The complex mixtures La RNAs include two previously sequenced 4.5S cells 5S ribosomal RNA-like All Ro possess 5-triphosphates. Some internal modifications typical transfer RNAs. RNPs are quite stable...
Signal recognition particle (SRP) is a ribonucleoprotein that functions in the targeting of ribosomes synthesizing presecretory proteins to ER. SRP binds signal sequence as it emerges from ribosome, and wheat germ extracts, arrests further elongation. The translation arrest released when interacts with its receptor on ER membrane. We show delay elongation mediated by not unique extracts. Addition mammalian reticulocyte lysates resulted preprolactin synthesis due increased ribosome pausing at...
Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24–60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated photosensitivity and cutaneous lesions these neonatal lupus, syndrome which mothers anti-Ro give birth to children complete congenital heart block photosensitive skin lesions. In higher eukaryotes, protein binds small RNAs unknown function known as Y RNAs. Because also misfolded 5S rRNA precursors, it is proposed...
We characterized the RNA-containing antigens precipitated by sera from 260 patients with positive antinuclear antibodies. 49 individuals, most of whom had systemic lupus erythematosus or Sjögren's syndrome, possessed antibodies that previously identified RNP, Sm, Ro, and La either singly in combinations. These antigens, which are located on discrete sets small nuclear cytoplasmic RNA-protein particles, exhibited a number antigenic interrelationships. One patient's serum recognized new...
Many bacteria contain an ortholog of the Ro autoantigen, a ring-shaped protein that binds noncoding RNAs (ncRNAs) called Y RNAs. In only studied bacterium, Deinococcus radiodurans, Rsr functions in heat-stress-induced ribosomal RNA (rRNA) maturation and starvation-induced rRNA decay. However, mechanism by which this conserved its associated ncRNAs act has been obscure. We report exoribonuclease polynucleotide phosphorylase (PNPase) form degradation machine is scaffolded RNA. Single-particle...
Transfer RNA fragments are proposed to regulate numerous processes in eukaryotes, including translation inhibition, epigenetic inheritance, and cancer. In the bacterium Salmonella enterica serovar Typhimurium, 5' tRNA halves ending 2',3' cyclic phosphate bind RtcR transcriptional activator, resulting transcription of an repair operon. However, since 3' can remain base paired after cleavage, could potentially as nicked tRNAs. Here we report that tRNAs ligands for RtcR. By isolating from...
The human autoantigen La is a 50-kDa protein which binds to the 3' termini of virtually all nascent polymerase III transcripts. Experiments with mammalian transcription extracts have led proposal that required for multiple rounds by RNA (E. Gottlieb and J. A. Steitz, EMBO 8:851-861, 1989; R. Maraia, D. Kenan, Keene, Mol. Cell. Biol. 14:2147-2158, 1994). Although homologs been identified in variety vertebrate species, has not invertebrates. In order begin genetic analysis function, we...