PXD044548 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Efficient Suppression of Premature Termination Codons by Engineered Chimeric 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 | 2025-05-06 |
AnnouncementXML | Submission_2025-05-06_07:36:37.725.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD044548 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Emma Doud |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-14 00:28:50 | ID requested | |
⏵ 1 | 2025-05-06 07:36:38 | 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] |
10.6019/PXD044548; |
Keyword List
submitter keyword: Suppressor transfer RNAs (sup-tRNAs),premature termination codons (PTCs),Pyrrolysine tRNA Scaffold Suppressor-tRNAs (PASS-tRNAs) |
Contact List
Amber Mosley |
contact affiliation | Indiana University School of Medicine |
contact email | almosley@iu.edu |
lab head | |
Emma Doud |
contact affiliation | Indiana University School of Medicine |
contact email | edoud@iu.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD044548 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044548
- Label: PRIDE project
- Name: Efficient Suppression of Premature Termination Codons by Engineered Chimeric Pyrrolysine tRNAs