A5066761237- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
University of North Carolina at Chapel Hill
2019-2025
UNC Lineberger Comprehensive Cancer Center
2019-2023
Segeberger Kliniken
2023
Columbus Center
2020
The Ohio State University
2017-2018
Cap homeostasis is a cyclical process of decapping and recapping that impacts portion the mRNA transcriptome. The metastable uncapped forms targets redistribute from polysomes to non-translating mRNPs, all needed for their return translating pool. Previous work identified cytoplasmic capping metabolon consisting enzyme (CE) 5′-monophosphate kinase bound adjacent domains Nck1. current study identifies canonical cap methyltransferase (RNMT) as responsible guanine-N7 methylation recapped mRNAs....
During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment Polycomb repressive complexes (PRCs) varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in trophoblast stem cells that induces long-range changes chromatin architecture coincide with PRC-directed modifications center around CpG island promoters contact locus even absence expression. Intensity between lncRNA...
Abstract Cap homeostasis is the cyclical process of decapping and recapping that maintains translation stability a subset transcriptome. Previous work showed levels some targets decline following transient expression an inactive form RNMT (ΔN-RNMT), likely due to degradation mRNAs with improperly methylated caps. The current study examined transcriptome-wide changes inhibition cytoplasmic cap methylation. This identified 5′-terminal oligopyrimidine (TOP) sequences as largest single class...
The Xist lncRNA requires Repeat A, a conserved RNA element located in its 5' end, to induce gene silencing during X-chromosome inactivation. Intriguingly, A is also required for production of Xist. While by the protein SPEN, how promotes remains unclear. We report that mouse embryonic stem cells, expression transgene comprising first two kilobases (Xist-2kb) causes transcriptional readthrough downstream polyadenylation sequences. Readthrough and ∼750 nucleotides downstream, did not require...
Scaffold attachment factor B (SAFB) is a conserved RNA-binding protein that essential for early mammalian development. However, the functions of SAFB in mouse embryonic stem cells (ESCs) have not been characterized. Using RNA immunoprecipitation followed by RNA-seq (RIP-seq), we examined RNAs associated with wild-type and SAFB/SAFB2 double-knockout ESCs. predominantly introns protein-coding genes through purine-rich motifs. The transcript most enriched association was lncRNA
Abstract We report that when expressed at similar levels from an isogenic locus, the Airn lncRNA induces Polycomb deposition with a potency rivals Xist . However, subject to same degree of promoter activation, is more abundant and potent than Our data definitively demonstrate functional suggest achieved extreme in part by evolving mechanisms promote its own abundance.
Xist requires Repeat-A, a protein-binding module in its first two kilobases (2kb), to repress transcription. We report that when expressed as standalone transcript mouse embryonic stem cells (ESCs), the 2kb of (Xist-2kb) does not induce transcriptional silencing. Instead, Xist-2kb sequesters RNA produced from adjacent genes on chromatin. Sequestration spread beyond genes, same sequence elements Repeat-A full-length transcription and can be induced by lncRNAs with similar composition...
Methyltransferases that methylate the guanine-N7 position of mRNA 5' cap structure are ubiquitous among eukaryotes and commonly encoded by viruses. Here we provide a detailed protocol for biochemical analysis RNA methyltransferase activity biological samples. This assay involves incubation cap-methyltransferase-containing samples with [32P]G-capped substrate S-adenosylmethionine (SAM) to produce RNAs N7-methylated caps. The extent methylation is then determined P1 nuclease digestion,...
ABSTRACT During mouse embryogenesis, expression of the lncRNA Airn induces gene silencing and recruits Polycomb Repressive Complexes (PRCs) to varying extents over a 15 megabase domain. The mechanisms remain unclear. Using high-resolution approaches, we show in trophoblast stem cells that long-range changes chromatin architecture coincide with PRC-directed modifications center around CpG island promoters contact locus even absence expression. Intensity between target correlated underlying...
Abstract The Xist lncRNA requires Repeat A, a conserved RNA element located in its 5′ end, to induce gene silencing during X-chromosome inactivation. Intriguingly, A is also required for the production of . While by protein SPEN, how promotes remains unclear. We report that mouse embryonic stem cells, expression transgene comprising first two kilobases ( -2kb) causes transcriptional readthrough multiple downstream polyadenylation sequences. Readthrough and ~750 nucleotides but did not...