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• W2782466730 abstract "Abstract Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide. Combining proteomics and transcriptomics allowed in depth platelet proteome characterization, revealing a significant effect of either stimulus on proteome composition. In silico analysis revealed the presence of resident immature RNAs in resting platelets, characterized by retained introns, while unbiased proteogenomics correlated intron removal by RNA splicing with changes on proteome composition upon activation. This allowed identification of a set of transcripts undergoing maturation by intron removal during activation and resulting in accumulation of the corresponding peptides at exon-exon junctions. These results indicate that RNA splicing events occur in platelets during activation and that maturation of specific pre-mRNAs is part of the activation cascade, contributing to a dynamic fine-tuning of the transcriptome." @default.
• W2782466730 created "2018-01-12" @default.
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• W2782466730 date "2018-01-11" @default.
• W2782466730 modified "2023-10-13" @default.
• W2782466730 title "Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications" @default.
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• W2782466730 doi "https://doi.org/10.1038/s41598-017-18985-5" @default.
• W2782466730 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5765118" @default.
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• W2782466730 hasPublicationYear "2018" @default.
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