A5006054489- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
Cornell University
2018-2022
The structural diversity of nucleic acid duplexes reflects the critical roles sequence, ions, and waters.
Significance RNA triple helices were characterized in vitro over 60 y ago, but only recently implicated diverse biological activities. The element for nuclear expression (ENE) protects from degradation via triplex formation with the poly(A) tail on 3ʹ ends of cellular RNAs. ENEs appear genomes, including a category containing two separated by double-stranded region (dENEs). Using structure probing, SAXS, and cryo-EM, we show that binding to rice dENE induces local conformational changes,...
The biological functions of RNA range from gene regulation through catalysis and depend critically on its structure flexibility. Conformational variations flexible, non-base-paired components, including hinges, bulges, or single-stranded tails, are well documented. Recent work has also identified in the ubiquitous, base-paired duplexes found almost all functional RNAs. Duplexes anchor structures folded RNAs, their surface features recognized by partner molecules. To date, no consistent...
RNA triple helices are commonly observed tertiary motifs that associated with critical biological functions, including signal transduction. Because the recognition of their importance is relatively recent, full range structural properties has not yet been elucidated. The integration solution wide-angle X-ray scattering (WAXS) molecular dynamics (MD) simulations, described here, provides a new way to capture structures major-groove triplexes evade crystallographic characterization. This...
Macromolecular structures can be determined from solution X-ray scattering. Small-angle scattering (SAXS) provides global structural information on length scales of 10s to 100s Ångstroms, and many algorithms are available convert SAXS data into low-resolution envelopes. Extension measurements wider angles (WAXS or wide-angle scattering) sharpen the resolution below 10 Å, filling in details that critical for biological function. These WAXS profiles especially challenging interpret because...
Like proteins, some RNAs fold to compact structures. We can model functional as a series of short, rigid, base-paired elements, connected by non-base-paired nucleotides that serve junctions. These connecting regions bend and twist, facilitating the formation tertiary contacts stabilize states. Here, we explore roles salt junction sequence in determining structures ubiquitous connector: an asymmetric internal loop. focus on J5/5a from widely studied P4–P6 domain Tetrahymena ribozyme....