Discovery of diverse chimeric peptides in a eukaryotic proteome sets the stage for experimental validation of the mosaic translation hypothesis

dc.authorid0000-0003-3636-1732
dc.authorid0000-0002-1471-7294
dc.authorid0000-0001-5973-3522
dc.authorid0000-0003-2835-3003
dc.contributor.authorCakir, Umut
dc.contributor.authorGabed, Noujoud
dc.contributor.authorKoroglu, Yunus Emre
dc.contributor.authorKaya, Selen
dc.contributor.authorSinharoy, Senjuti
dc.contributor.authorBenedito, Vagner A.
dc.contributor.authorBrunet, Marie
dc.date.accessioned2026-02-03T12:02:46Z
dc.date.available2026-02-03T12:02:46Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractThe high complexity of eukaryotic organisms enabled their evolutionary success, driven by the diversification of their proteomes. Various mechanisms contributed to this process. Alternative splicing had the largest known impact among these mechanisms. Earlier, we hypothesized that along with alternative splicing, a different but conceptually similar mechanism creates novel versions of existing proteins in all eukaryotes. However, this mechanism operates at the level of translation, where amino acid sequence novelty arises through multiple programmed ribosomal frameshifting events occurring within the same transcript. This mechanism, which is termed mosaic translation, is very difficult to demonstrate even with the most up-to-date molecular tools. Thus, it remained unnoticed so far. Using a subset of mass spectrometry proteomic data from various organs of the model plant Medicago truncatula, we took the first step toward experimental validation of this hypothesis. Our original in silico approach resulted in the discovery of two candidates for mosaic proteins (homologs of EF1 alpha and RuBisCo) and 154 candidates for chimeric peptides. Chimeric peptides and polypeptides are produced in the course of one ribosomal frameshifting event and may correspond to parts of mosaic proteins. In addition, our analysis reveals the possibility of translation of chimeric peptides from five ribosomal RNA transcripts, ten long non-coding RNA transcripts, and one transfer RNA transcript. These findings are novel and will form the basis for future experimental validation. We also present multiple lines of indirect evidence supporting the validity of our in silico data.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) grants
dc.description.sponsorshipBogazici University standard research grant (BAP-P) [TUBITAK 1001 120Z514, TUBITAK 1002 120Z247, BAP-P 18841]
dc.description.sponsorshipCanada Research Chair in Functional Proteomics and Discovery of Novel Proteins
dc.description.sponsorshipCanadian Institutes of Health Research Project Grant [PJT-175322]
dc.description.sponsorshipFonds de Recherche du Quebec en Sante (FRQS) Junior 1 award [307936]
dc.description.sponsorshipUnited Arab Emirates University
dc.description.sponsorshipUC from the IMPRS-Genome Science PhD program
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) grants and Bogazici University standard research grant (BAP-P) to UC and IK (TUBITAK 1001 120Z514, TUBITAK 1002 120Z247, and BAP-P 18841), a Canada Research Chair in Functional Proteomics and Discovery of Novel Proteins to XR, and a Canadian Institutes of Health Research Project Grant PJT-175322 to XR and MB. MB was supported by a Fonds de Recherche du Quebec en Sante (FRQS) Junior 1 award (307936). Computational analysis was conducted using the server of the Turkish National e-Science e-Infrastructure (TRUBA) center. The completion of this study was made possible by support for IK from United Arab Emirates University and for UC from the IMPRS-Genome Science PhD program.
dc.identifier.doi10.1016/j.csbj.2025.09.019
dc.identifier.endpage4064
dc.identifier.issn2001-0370
dc.identifier.pmid41035503
dc.identifier.scopus2-s2.0-105016085717
dc.identifier.scopusqualityQ1
dc.identifier.startpage4048
dc.identifier.urihttps://doi.org/10.1016/j.csbj.2025.09.019
dc.identifier.urihttps://hdl.handle.net/20.500.12428/34864
dc.identifier.volume27
dc.identifier.wosWOS:001575285200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofComputational and Structural Biotechnology Journal
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260130
dc.subjectChimeric peptide
dc.subjectProgrammed ribosomal frameshifting
dc.subjectAlternative open reading frame
dc.subjectElongation factor
dc.subjectRuBisCo
dc.subjectMosaic translation
dc.titleDiscovery of diverse chimeric peptides in a eukaryotic proteome sets the stage for experimental validation of the mosaic translation hypothesis
dc.typeArticle

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