MicroRNAs as Modulators of the Platelet Proteome

Patricia      Landry; Patrick      Provost

doi:10.2174/157016411797247468

Abstract

MicroRNAs are short 21- to 24-nucleotide (nt) RNA species that act as key regulators of gene expression. Known primarily to modulate mRNA translation through recognition of specific binding sites located in the 3untranslated region (UTR) of messenger RNA (mRNA) targets, microRNAs may regulate between 30% to 92% of the genes in human, thereby controlling a plethora of biological processes. Although devoid of a nucleus and lacking genomic DNA, platelets may be no exception, as recent experimental evidences indicate that they contain all the protein and RNA components and features required for microRNA-regulated mRNA translation: (i) the platelet transcriptome is astonishingly diverse, representing between 15 and 32% of all human genes, (ii) platelet mRNAs can be translated into proteins, (iii) platelets contain an abundant and diverse array of microRNAs, and (iv) the host Dicer and Argonaute 2 (Ago2) complexes. The latter ones are functional in microRNA biogenesis and function, respectively. In this review article, we will summarize and discuss the experimental evidences as well as the most recent advances supporting a role for microRNAs as modulators of the platelet proteome. Expected to play a central role in health and disease, a dysfunctional microRNA-based regulation of gene expression in platelets may represent an important etiologic factor underlying platelet-related and cardiovascular diseases.

Keywords: Cardiovascular diseases, gene regulation, messenger RNA, microRNA, RNA silencing, platelet, biogenesis, nuclear ribonuclease, mutation, neurological diseases