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Nuclei of HeLa cells interactomes unravel a network of ghost proteins involved in proteins translation

Abstract : Ghost proteins are issued from alternative Open Reading Frames (ORFs) and are missing a genome annotation. Indeed, historical filters applied for the detection of putative translated ORFs led to a wrong classification of transcripts considered as non-coding although translated proteins can be detected by proteomics. This Ghost (also called Alternative) proteome was neglected, and one major issue is to identify the implication of the Ghost proteins in the biological processes. In this context, we aimed to identify the protein-protein interactions (PPIs) of the Ghost proteins. For that, we re-explored a cross-link MS study performed on nuclei of HeLa cells using cross-linking mass spectrometry (XL-MS) associated with the HaltOrf database. Among 1679 cross-link interactions identified, 292 are involving Ghost Proteins. Forty-Four of these Ghost proteins are found to interact with 7 Reference proteins related to ribonucleoproteins, ribosome subunits and zinc finger proteins network. We, thus, have focused our attention on the heterotrimer between the RE/poly(U)-binding/degradation factor 1 (AUF1), the Ribosomal protein 10 (RPL10) and AltATAD2. Using I-Tasser software we performed docking models from which we could suggest the attachment of AUF1 on the external part of RPL10 and the interaction of AltATAD2 on the RPL10 region interacting with 5S ribosomal RNA as a mechanism of regulation of the ribosome. Taken together, these results reveal the importance of Ghost Proteins within known protein interaction networks.
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Submitted on : Wednesday, July 20, 2022 - 12:22:44 PM
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Tristan Cardon, Michel Salzet, Julien Franck, Isabelle Fournier. Nuclei of HeLa cells interactomes unravel a network of ghost proteins involved in proteins translation. Biochimica et Biophysica Acta (BBA) - General Subjects, Elsevier, 2019, 1863 (10), pp.1458-1470. ⟨10.1016/j.bbagen.2019.05.009⟩. ⟨inserm-02941645⟩



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