- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
University of North Carolina at Chapel Hill
2019-2025
RNA structure and dynamics are critical to biological function. However, strategies for determining in vivo limited, with established chemical probing newer duplex detection methods each having deficiencies. Here we convert the common reagent dimethyl sulfate into a useful probe of all 4 nucleotides. Building on this advance, introduce PAIR-MaP, which uses single-molecule correlated directly detect base-pairing interactions cells. PAIR-MaP has superior resolution compared alternative...
Translational reprogramming allows organisms to adapt changing conditions. Upstream start codons (uAUGs), which are prevalently present in mRNAs, have crucial roles regulating translation by providing alternative sites1-4. However, what determines this selective initiation of between conditions remains unclear. Here, integrating transcriptome-wide translational and structural analyses during pattern-triggered immunity Arabidopsis, we found that transcripts with immune-induced enriched...
Abstract Chemical probing technologies enable high-throughput examination of diverse structural features RNA, including local nucleotide flexibility, RNA secondary structure, protein and ligand binding, through-space interaction networks, multistate ensembles. Deep understanding structure–function relationships typically requires evaluating a system under structure- function-altering conditions, linking these data with additional information, visualizing multilayered relationships. Current...
ABSTRACT RNAs are critical regulators of gene expression, and their functions often mediated by complex secondary tertiary structures. Structured regions in RNA can selectively interact with small molecules – via well-defined ligand binding pockets to modulate the regulatory repertoire an RNA. The broad potential biological function intentionally RNA-ligand interactions remains unrealized, however, due challenges identifying compact motifs ability bind ligands good physicochemical properties...
Many lncRNAs have been discovered using transcriptomic data; however, it is unclear what fraction of functional and structural properties affect their phenotype. MUNC lncRNA (also known as DRReRNA) acts an enhancer RNA for the Myod1 gene in cis stimulates expression other promyogenic genes trans by recruiting cohesin complex. Here, experimental probing structure revealed that contains multiple domains not detected prediction algorithms absence information. We show these specific structurally...
Abstract Chemical probing technologies enable high-throughput examination of diverse structural features RNA including local nucleotide flexibility, secondary structure, protein- and ligand-binding, through-space interaction networks, multi-state ensembles. Performing these experiments, by themselves, does not directly lead to biological insight. Instead, deep understanding structure-function relationships typically requires evaluating a system under structure- function-altering conditions,...
Single-molecule correlated chemical probing (smCCP) is an experimentally concise strategy for characterizing higher-order structural interactions in RNA. smCCP data yield rich, but complex, information about base pairing, conformational ensembles, and tertiary interactions. To date, through-space communication specifically measuring RNA structure has been difficult to isolate from reflective of other Here, we introduce mutual as a filtering metric contained within use this characterize the...
Abstract Our group recently discovered that the circular RNA (circRNA), CDR1as, promotes lung cancer metastasis in part through stabilization of coding gene, CDR1. The purpose this study was to identify intramolecular secondary structures CDR1as and determine whether there is a functional relationship between structure non-small cell (NSCLC) metastasis. We employed chemical probing approach selective 2’- hydroxyl acylation analyzed by primer extension mutational profiling (SHAPE-MaP)...
Abstract Biogenesis of circular RNA usually involves a backsplicing reaction where the downstream donor site is ligated to upstream acceptor by spliceosome. For this occur, it hypothesized that these sites must be in proximity. Inverted repeat sequences, such as Alu elements, and introns are predicted base-pair represent one mechanism for inducing Here, we investigate pre-mRNA structure human HIPK3 gene at exon 2, which forms via backsplicing. We leverage multiple chemical probing...
ABSTRACT RNA structure and dynamics are critical to biological function. However, strategies for determining in vivo limited, with established chemical probing newer duplex detection methods each having notable deficiencies. Here we convert the common reagent dimethyl sulfate (DMS) into a useful probe of all four nucleotides. Building on this advance, introduce PAIR-MaP, which uses single-molecule correlated directly detect base pairing interactions cells. PAIR-MaP has superior resolution...
Summary Many lncRNAs have been discovered using transcriptomic data, however, it is broadly unclear what fraction of are functional and structural properties affect their phenotype. MUNC lncRNA, also known as DRR eRNA, stimulates skeletal muscle differentiation. The prevailing hypothesis that the Myod1 gene in cis an enhancer RNA expression several other promyogenic genes trans by recruiting cohesin complex to promoters. Experimental probing structure revealed contains multiple domains not...
ABSTRACT To survive stress, eukaryotes selectively translate stress-related transcripts while inhibiting growth-associated protein production. How this translational reprogramming occurs under biotic stress has not been systematically studied. identify common features shared by with stress-upregulated translation efficiency (TE-up), we first performed high-resolution ribosome-sequencing in Arabidopsis during pattern-triggered immunity and found that TE-up are enriched upstream open reading...