A5059313169- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Neurogenesis and neuroplasticity mechanisms
- Biochemical and Molecular Research
- Genomics and Phylogenetic Studies
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
National Cancer Institute
2012-2025
National Institutes of Health
2014-2024
Center for Cancer Research
2011-2024
Frederick National Laboratory for Cancer Research
2011-2012
Cancer Genetics (United States)
2011-2012
Frederick Community College
2012
Harvard University
2008-2011
Boston Children's Hospital
2011
Broad Institute
2008
Massachusetts Institute of Technology
2008
Nuclear factor of activated T cells (NFAT) proteins are Ca 2+ -regulated transcription factors that control gene expression in many cell types. NFAT heavily phosphorylated and reside the cytoplasm resting cells; when stimulated by a rise intracellular , dephosphorylated / calmodulin -dependent phosphatase calcineurin translocate to nucleus activate target expression. Here we show NFAT1 is present large cytoplasmic RNA-protein scaffold complex contains long intergenic noncoding RNA (lincRNA),...
The transition from naïve to activated T cells is marked by alternative splicing of pre-mRNA encoding the transmembrane phosphatase CD45. Using a short hairpin RNA interference screen, we identified heterogeneous ribonucleoprotein L-like (hnRNPLL) as critical inducible regulator CD45 splicing. HnRNPLL was up-regulated in stimulated cells, bound transcripts, and both necessary sufficient for Depletion or overexpression hnRNPLL B cell lines primary resulted reciprocal alteration CD45RA RO...
N4-acetylcytidine (ac4C) is a highly conserved modified RNA nucleobase whose formation catalyzed by the disease-associated N-acetyltransferase 10 (NAT10). Here we report sensitive chemical method to localize ac4C in RNA. Specifically, characterize susceptibility of borohydride-based reduction and show this reaction can cause introduction noncognate base pairs during reverse transcription (RT). Combining borohydride-dependent misincorporation with ac4C's known base-sensitivity provides unique...
The human acetyltransferase NAT10 has recently been shown to catalyze formation of N4-acetylcytidine (ac4C), a minor nucleobase known alter RNA structure and function. In order better understand the role acetyltransferases in biology disease, here we report development application chemical methods study ac4C. First, demonstrate that ac4C can be conjugated carrier proteins using optimized protocols. Next, describe access ac4C-containing RNAs, enabling screening anti-ac4C antibodies. Finally,...
Brain-derived neurotrophic factor (BDNF) is a potent modulator of brain synaptic plasticity. Signaling defects caused by dysregulation its Ntrk2 (TrkB) kinase (TrkB.FL) and truncated receptors (TrkB.T1) have been linked to the pathophysiology several neurological neurodegenerative disorders. We found that upregulation Rbfox1, an RNA binding protein associated with intellectual disability, epilepsy autism, increases selectively hippocampal TrkB.T1 isoform expression. Physiologically,...
DNA methylome analysis in a variety of species has revealed elevated 5-methylcytosine at exons relative to introns. These associations raised the possibility that intragenic methylation aids spliceosome process exon definition. Here, I highlight recent genome-wide and direct evidence linking pre-mRNA splicing.
B cells and plasma possess distinct RNA processing environments that respectively promote the expression of membrane-associated Ig by versus secretion cells. Through a combination transcriptional profiling screening using lentiviral short-hairpin interference library, we show both splicing factor hnRNPLL transcription elongation ELL2 modulate ratio secreted membrane-encoding Ighg2b transcripts in MPC11 plasmacytoma cell lines. are highly expressed primary relative to cells, but binds mRNA...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death worldwide, underscoring urgent need to uncover its molecular underpinnings and develop novel therapeutic targets. Over 170 RNA modifications constitute epitranscriptome. Notably, chemical modification N4-acetylcytidine (ac4C) writer enzyme, N-acetyltransferase 10 (NAT10), are overexpressed in most solid tumors, including pancreatic cancer, with high NAT10 expression correlating worse...
The mechanisms supporting dynamic regulation of CTCF-binding sites remain poorly understood. Here we describe the TET-catalyzed 5-methylcytosine derivative, 5-carboxylcytosine (5caC), as a factor driving new CTCF binding within genomic DNA. Through combination in vivo and vitro approaches, reveal that 5caC generally strengthens association with DNA facilitates to suboptimal sequences. Dramatically, profiling cellular model accumulates identified ~13,000 sites. were enriched for overlapping...
N4-acetylcytidine (ac4C) is an mRNA modification catalyzed by the enzyme N-acetyltransferase 10 (NAT10), with position-dependent effects on translation. This protocol details a procedure to map ac4C at base resolution using NaBH4-induced reduction of and conversion thymidine followed sequencing (RedaC:T-seq). Total RNA ribodepleted then treated NaBH4 reduce tetrahydro-ac4C, which specifically alters pairing during cDNA synthesis, allowing detection positions called as following Illumina...
Generation of the epitranscriptome through chemical modifications protein-coding messenger RNAs (mRNAs) has emerged as a new mechanism post-transcriptional gene regulation. While most mRNA are methylation events, single acetylated ribonucleoside been described in eukaryotes, occurring at N4-position cytidine (N4-acetylcytidine or ac4C). Using combination antibody-based enrichment regions and deep sequencing, we recently reported ac4C novel modification that is catalyzed by...
The functional analysis of epitranscriptomic modifications in RNA is constrained by a lack methods that accurately capture their locations and levels. We previously demonstrated the modification N4-acetylcytidine (ac4C) can be mapped at base resolution through sodium borohydride reduction to tetrahydroacetylcytidine (tetrahydro-ac4C), followed cDNA synthesis misincorporate adenosine opposite reduced ac4C sites, culminating C:T mismatches acetylated cytidines (RedaC:T). However, this process...