A5067949959- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Immunology Research
- Polyamine Metabolism and Applications
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
Yale University
2020-2024
An intriguing consequence of ongoing riboswitch discovery efforts is the occasional identification metabolic or toxicity response pathways for unusual ligands. Recently, we reported experimental validation three distinct bacterial classes that regulate gene expression in to selective binding a guanidinium ion. These classes, called guanidine-I, -II, and -III, numerous genes whose protein products include previously misannotated guanidine exporters enzymes degrade via an initial carboxylation...
Over the past three decades, researchers have found that some engineered aptamers can be made to work well in test tubes but these same might fail function cells. To help address this problem, we developed 'Graftamer' approach, an experimental platform exploits architecture of a natural riboswitch enhance vitro aptamer selection and accelerate vivo testing. Starting with combinatorial RNA pools contain structural features guanine interspersed regions random sequence, performed multiplexed...
Natural polyamines such as spermidine and spermine cations have characteristics that make them highly likely to be sensed by riboswitches, their general affinity polyanionic RNA broad contributions cell physiology. Despite previous claims polyamine riboswitches exist, evidence of biological functions has remained unconvincing. Here, we report rare variants bacterial S-adenosylmethionine-I (SAM-I) reject SAM adapted selectively sense spermidine. These spermidine-sensing riboswitch are...
Drug candidates that fail in clinical trials for efficacy reasons might still have favorable safety and bioavailability characteristics could be exploited. A failed drug candidate repurposed if a receptor, such as an aptamer, were created binds the compound with high specificity. Branaplam is small molecule was previously development to treat spinal muscular atrophy Huntington's disease. Here, we report of (48-nucleotide) RNA aptamer branaplam dissociation constant ∼150 nM. Starting...
ABSTRACT An intriguing consequence of ongoing riboswitch discovery efforts is the occasional identification metabolic or toxicity response pathways for unusual ligands. Recently, we reported experimental validation three distinct bacterial classes that regulate gene expression in to selective binding a guanidinium ion. These classes, called guanidine-I, -II and -III, numerous genes whose protein products include previously misannotated guanidine exporters enzymes degrade via an initial...