PXD044322 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Efficient Suppression of Premature Termination Codons by Engineered Pyrrolysine tRNAs |
Description | Mutations that introduce premature termination codons (PTCs) within protein-coding genes are associated with incurable and severe genetic diseases. Many PTC-associated disorders are life-threatening and have no approved medical treatment options. Suppressor transfer RNAs (sup-tRNAs) with the capacity to promote translational readthrough of PTCs represent a promising therapeutic strategy to treat these conditions; however, developing novel sup-tRNAs with high efficiency and specificity often requires extensive engineering and screening. Moreover, these efforts are not always successful at producing more efficient sup-tRNAs. Here we show that the pyrrolysine tRNA (tRNAPyl), which naturally translates the UAG stop codon, offers an attractive scaffold for developing potent sup-tRNAs that restore protein synthesis from PTC-containing genes. We created a series of rationally designed Pyrrolysine tRNA Scaffold Suppressor-tRNAs (PASS-tRNAs) that are substrates of bacterial and human alanyl-tRNA synthetase. Using a PTC-containing reporter gene, PASS-tRNAs restore protein synthesis to wild-type levels in bacterial cells. In human cells, PASS-tRNAs display robust and consistent translation activity in two distinct PTC reporter genes with high codon specificity and no observed cytotoxic effects. Collectively, these results unveil a new class of highly efficient sup-tRNAs with great potential for tRNA-based therapeutics. |
HostingRepository | PRIDE |
AnnounceDate | 2025-02-20 |
AnnouncementXML | Submission_2025-02-20_07:20:40.080.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jeremy Balsbaugh |
SpeciesList | scientific name: Escherichia coli; NCBI TaxID: 562; |
ModificationList | acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-03 07:59:14 | ID requested | |
⏵ 1 | 2025-02-20 07:20:40 | announced | |
Publication List
10.1093/nar/gkae1048; |
Awawdeh A, Tapia A, Alshawi SA, Dawodu O, Gaier SA, Specht C, Beaudoin JD, Tharp JM, Vargas-Rodriguez O, Efficient suppression of premature termination codons with alanine by engineered chimeric pyrrolysine tRNAs. Nucleic Acids Res, 52(22):14244-14259(2024) [pubmed] |
Keyword List
submitter keyword: proteomics,mutations, premature termination codons, tRNA, bacteria, GFP |
Contact List
Jeremy Balsbaugh |
contact affiliation | Proteomics & Metabolomics Facility, University of Connecticut |
contact email | jeremy.balsbaugh@uconn.edu |
lab head | |
Jeremy Balsbaugh |
contact affiliation | University of Connecticut |
contact email | jeremy.balsbaugh@uconn.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044322
- Label: PRIDE project
- Name: Efficient Suppression of Premature Termination Codons by Engineered Pyrrolysine tRNAs