Significance: Levels of platelet noncoding RNAs (ncRNAs) are altered by disease, and ncRNAs may exert functions inside and outside of platelets. Their role in physiologic hemostasis and pathologic thrombosis remains to be explored. Recent Advances: The number of RNA classes identified in platelets has been growing since the past decade. Apart from coding messenger RNAs, the RNA landscape in platelets comprises ncRNAs such as microRNAs, circular RNAs, long ncRNAs, YRNAs, and potentially environmentally derived exogenous ncRNAs. Recent research has focused on the function of platelet RNAs beyond platelets, mediated through protective RNA shuttles or even cellular uptake of entire platelets. Multiple studies have also explored the potential of platelet RNAs as novel biomarkers. Critical Issues: Platelet preparations can contain contaminating leukocytes. Even few leukocytes may contribute a substantial amount of RNA. As biomarkers, platelet RNAs have shown associations with platelet activation, but it remains to be seen whether their measurements could improve diagnostics. It also needs to be clarified whether platelet RNAs influence processes beyond platelets. Future Directions: Technological advances such as single-cell RNA-sequencing might help to identify hyperreactive platelet subpopulations on a single-platelet level, avoid the common problem of leukocyte contamination in platelet preparations, and allow simultaneous profiling of native megakaryocytes and their platelet progeny to clarify to what extent the platelet RNA content reflects their megakaryocyte precursors or changes in the circulation. Antioxid. Redox Signal. 34, 1200-1216.
Keywords: biomarker; megakaryocyte; noncoding RNA; platelet; platelet inhibitor.