Preprint
Engineered transfer RNAs for suppression of premature termination codons
bioRxiv: the preprint server for biology
Cold Spring Harbor Laboratory
08/27/2018
DOI: 10.1101/400127
Abstract
Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. We present a high-throughput, cell-based assay to identify a nti c odon e ngineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identified ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo , producing PTC repair in multiple genes, including disease causing mutations within the cystic fibrosis transmembrane conductance regulator ( CFTR ).
Details
- Title: Subtitle
- Engineered transfer RNAs for suppression of premature termination codons
- Creators
- John D LueckJae Seok YoonAlfredo Perales-PuchaltAdam L MackeyDaniel T InfieldMark A BehlkeMarshall R PopeDavid B WeinerWilliam R SkachPaul B McCray JrChristopher A Ahern
- Resource Type
- Preprint
- Publication Details
- bioRxiv: the preprint server for biology
- DOI
- 10.1101/400127
- Publisher
- Cold Spring Harbor Laboratory
- Language
- English
- Date posted
- 08/27/2018
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medicine Administration; Internal Medicine
- Record Identifier
- 9984071626202771
Metrics
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