title: Megakaryocytes differentially sort mRNAs for matrix metalloproteinases and their inhibitors into platelets: a mechanism for regulating synthetic events.
abstract: Megakaryocytes transfer a diverse and functional transcriptome to platelets during the final stages of thrombopoiesis. In platelets, these transcripts reflect the expression of their corresponding proteins and, in some cases, serve as a template for translation. It is not known, however, if megakaryocytes differentially sort mRNAs into platelets. Given their critical role in vascular remodeling and inflammation, we determined whether megakaryocytes selectively dispense transcripts for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) into platelets. Next-generation sequencing (RNA-Seq) revealed that megakaryocytes express mRNA for 10 of the 24 human MMP family members. mRNA for all of these MMPs are present in platelets with the exception of MMP-2, 14, and 15. Megakaryocytes and platelets also express mRNA for TIMPs 1-3, but not TIMP-4. mRNA expression patterns predicted the presence and, in most cases, the abundance of each corresponding protein. Nonetheless, exceptions were observed: MMP-2 protein is present in platelets but not its transcript. In contrast, quiescent platelets express TIMP-2 mRNA but only traces of TIMP-2 protein. In response to activating signals, however, platelets synthesize significant amounts of TIMP-2 protein. These results demonstrate that megakaryocytes differentially express mRNAs for MMPs and TIMPs and selectively transfer a subset of these into platelets. Among the platelet messages, TIMP-2 serves as a template for signal-dependent translation.
authors.affiliation: Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cecchetti
authors.forename: Neal D
authors.initials: ND
authors.lastname: Tolley
authors.forename: Noemi
authors.initials: N
authors.lastname: Michetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Bury
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases