Proteomics

Dataset Information

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Proteogenomics of ex vivo-activated platelets.


ABSTRACT: Platelets are major players in the process of intravascular thrombus formation. Current therapeutic strategies still fail to prevent thrombotic coronary events in a substantial number of patients, indicating that the complex mechanisms modulating platelet response during activation are not fully elucidated. The evidence that platelets are capable of de novo protein synthesis has raised the issue of whether and how these resident mRNAs are regulated in circulating platelets. Among the several mechanisms potentially involved, mRNA splicing may be relevant. Purified platelet-rich plasmas from healthy volunteers were collected and in vitro activated with collagen or Thrombin Receptor Activating Peptide (TRAP). Transcriptome profiling by RNA-Seq and in silico intron representation analysis were applied to search for the presence of pre-mRNA molecules and splicing events affected by platelet activation. HiRIEF LC-MS allowed platelet proteome characterization at deep coverage to investigate a possible correlation between splicing events and protein levels. By comparing computational and wet-lab analyses it was possible to identify a set of transcripts influenced at both intron and protein level.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Mattias Vesterlund  

LAB HEAD: Janne Lehtiö

PROVIDER: PXD006559 | Pride | 2018-01-03

REPOSITORIES: Pride

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Publications

Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications.

Nassa Giovanni G   Giurato Giorgio G   Cimmino Giovanni G   Rizzo Francesca F   Ravo Maria M   Salvati Annamaria A   Nyman Tuula A TA   Zhu Yafeng Y   Vesterlund Mattias M   Lehtiö Janne J   Golino Paolo P   Weisz Alessandro A   Tarallo Roberta R  

Scientific reports 20180111 1


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.  ...[more]

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