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PXD044322

PXD044322 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEfficient Suppression of Premature Termination Codons by Engineered Pyrrolysine tRNAs
DescriptionMutations 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.
HostingRepositoryPRIDE
AnnounceDate2025-02-20
AnnouncementXMLSubmission_2025-02-20_07:20:40.080.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeremy Balsbaugh
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationListacetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-03 07:59:14ID requested
12025-02-20 07:20:40announced
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 affiliationProteomics & Metabolomics Facility, University of Connecticut
contact emailjeremy.balsbaugh@uconn.edu
lab head
Jeremy Balsbaugh
contact affiliationUniversity of Connecticut
contact emailjeremy.balsbaugh@uconn.edu
dataset submitter
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Dataset FTP location
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