Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds
| Main Author: | |
|---|---|
| Language: | English |
| Published: |
Bowling Green State University / OhioLINK
2010
|
| Subjects: | |
| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1288300501 |
| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-bgsu1288300501 |
|---|---|
| record_format |
oai_dc |
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-bgsu12883005012021-08-03T05:29:32Z Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds Novikova, Irina V. Chemistry tecto-RNA receptor-loop motifs paranemic motifs nanotechnology <p>RNA has favorable properties for use as a medium for constructing multivalent, modular nanoparticles to deliver therapeutic agents targeting virus-infected or cancer cells or for serving as scaffolds to organize the matter at nanoscale. RNA nanoparticles possessing diverse functionalities can be engineered to self-associate via interaction motifs to increase their in vivo stability and propensity for cellular uptake or form various materials of fibrous architecture.</p><p>High affinity and specificity RNA-RNA binding interfaces can be constructed by combining pairs of GNRA loop/loop-receptor interaction motifs. By fusing these RNA interactions and 4-way junction motifs, we have developed tecto-RNA complexes possessing favorable properties for drug delivery applications such as enhanced nuclease protection and hetero-multimerization amenability desirable for multi-functionality aims. We demonstrated that these RNA molecules can be programmed for uncompensated assembly to form closed, ring-shaped complexes of defined and predictable stoichiometries that assemble cooperatively. We provided a step-by-step description how the stoichiometry can be controlled at the RNA monomer level from ring-closed dimeric, trimeric and tetrameric complexes to polymeric structures where ring formation is no longer possible. Structure-probing studies of optimally designed dimer and trimer complexes provided strong experimental evidence that RNA systems self-associate as intended by design. Detailed thermodynamic analysis of tecto-RNA self-assembly allowed us to disclose the binding affinities, to quantify the cooperativity of assembly and to elucidate the energy of four-way junction conformational adjustments for interaction.</p><p>Alternative interaction motifs such as paranemic crossover (PX) motifs provide specific, programmable and reversible binding interactions between pre-folded nucleic acid molecules. We explored their potential for RNA biosensing and RNA nanotechnology applications. Sequence-specific, label-free RNA biosensors targeting pre-folded internal loop motifs were constructed by coupling paranemic binding motifs to a Malachite Green aptamer. We showed that this binding is sequence-specific as single-basepair mismatches in the paranemic binding motif disrupt the sensor-target interaction. We also explored the use of the paranemic motif as a cohesion tool for engineering linear RNA fibrils and for recognition of asymmetric, artificially-designed and natural internal loops.</p> 2010-11-18 English text Bowling Green State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1288300501 http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1288300501 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Chemistry tecto-RNA receptor-loop motifs paranemic motifs nanotechnology |
| spellingShingle |
Chemistry tecto-RNA receptor-loop motifs paranemic motifs nanotechnology Novikova, Irina V. Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| author |
Novikova, Irina V. |
| author_facet |
Novikova, Irina V. |
| author_sort |
Novikova, Irina V. |
| title |
Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| title_short |
Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| title_full |
Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| title_fullStr |
Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| title_full_unstemmed |
Paranemic and Receptor-Loop RNA Motifs: Versatile Interactions for Biosensing Platforms and Nanotechnology Scaffolds |
| title_sort |
paranemic and receptor-loop rna motifs: versatile interactions for biosensing platforms and nanotechnology scaffolds |
| publisher |
Bowling Green State University / OhioLINK |
| publishDate |
2010 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1288300501 |
| work_keys_str_mv |
AT novikovairinav paranemicandreceptorlooprnamotifsversatileinteractionsforbiosensingplatformsandnanotechnologyscaffolds |
| _version_ |
1719420823596433408 |