A5014715222- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- Enzyme Structure and Function
- MicroRNA in disease regulation
- Biotin and Related Studies
- Cancer-related molecular mechanisms research
- Click Chemistry and Applications
University of North Carolina at Chapel Hill
2012-2021
Novartis (United States)
2018
RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures riboswitch aptamers and puzzle 7, ribozyme structure, are included this the experiment. The include biological binding sites for small molecules ( S -adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5′-triphosphate, glutamine) proteins (YbxF), one set describes large conformational...
RNA secondary structure modeling is a challenging problem, and recent successes have raised the standards for accuracy, consistency, tractability. Large increases in accuracy been achieved by including data on reactivity toward chemical probes: Incorporation of 1M7 SHAPE into an mfold-class algorithm results median accuracies base pair prediction that exceed 90%. However, few structures are modeled with significantly lower accuracy. Here, we show incorporating differential reactivities from...
Many RNA structures are composed of simple secondary structure elements linked by a few critical tertiary interactions. SHAPE chemistry has made interrogation dynamics at single-nucleotide resolution straightforward. However, de novo identification nucleotides involved in interactions remains challenge. Here we show that form noncanonical or contacts can be detected comparing information obtained using two reagents, N-methylisatoic anhydride (NMIA) and 1-methyl-6-nitroisatoic (1M6)....
Higher-order structure governs function for many RNAs. However, discerning this large RNA molecules in solution is an unresolved challenge. Here, we present SHAPE-JuMP (selective 2'-hydroxyl acylation analyzed by primer extension and juxtaposed merged pairs) to interrogate through-space tertiary interactions. A bifunctional small molecule used chemically link proximal nucleotides structure. The cross-link site then encoded into complementary DNA (cDNA) a single, direct step using engineered...
Eukaryotic genomes produce RNAs lacking protein-coding potential, with enigmatic roles. We integrated three approaches to study large intervening noncoding RNA (lincRNA) gene functions. First, we profiled mouse embryonic stem cells and neural precursor at single-cell resolution, revealing lincRNAs expressed in specific cell types, subpopulations, or cycle stages. Second, assembled a transcriptome-wide atlas of nuclear lincRNA degradation by identifying targets the exosome cofactor Mtr4....
The ribosome moves between distinct structural states and is organized into multiple functional domains. Here, we examined hundreds of occurrences pairwise through-space communication nucleotides in the small subunit RNA using interaction groups analyzed by mutational profiling (RING-MaP) single-molecule correlated chemical probing bacterial cells. RING-MaP revealed four communities RNA, each from organization defined secondary structure. head domain contains 2 communities: outer-head pivot...
We introduce a melded chemical and computational approach for probing modeling higher-order intramolecular tertiary interactions in RNA. 2'-Hydroxyl molecular interference (HMX) identifies nucleotides highly packed regions of an RNA by exploiting the ability bulky adducts at 2'-hydroxyl position to disrupt overall structure. HMX was found be exceptionally selective quantitative detection interactions. When incorporated as experimental constraints discrete dynamics simulations, information...