The Power of mRNA in Anucleate Platelets

Graphic- The Power of mRNA in Anucleate Platelets
During the process of platelet formation, megakarycoytes transfer RNA-processing machinery and thousands of mRNAs, which code for thromboinflammatory protein products that regulate human diseases.

Platelets are the smallest cell in the bloodstream, and one of the few anucleate cells (i.e., cells that circulate without a nucleus). Because of their small size and anucleate stature, platelets have historically been conceived of as “sacs of glue” that function solely to stop bleeding. Andrew Weyrich, MD, and his group made the seminal discovery that anucleate human platelets transform messenger RNA (mRNA) into mature products that code for protein. More recently, his group found that a specific type of microRNAs (Dicer1-dependent) and their precursors (megakaryocytes) modulate the expression of target mRNAs important for cellular function.

These observations revolutionized the field of hematology, leading to an explosion of studies that use mRNA profiling to identify previously-unrecognized functions of megakaryocytes and platelets that regulate thrombosis and inflammation (i.e., thromboinflammation). This work has also advanced scientific understanding of non-traditional functions of platelets that regulate the course of numerous diseases, including cardiovascular disease, diabetes, and infectious syndromes.  

References:

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Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, Yost CC, Rubner FJ, Albertine KH, Swoboda KJ, Fratto CM, Tolley E, Kraiss LW, McIntyre TM, Zimmerman GA, Weyrich AS. Cell. 2005 August 12;122(3):379. 

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Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Rowley JW, Chappaz S, Corduan A, Chong MMW, Campbell RA, Khoury A, Manne BK, Wurtzel JGT, Michael JV, Goldfinger LE, Mumaw MM, Nieman MT, Kile BT, Provost P, Weyrich AS.  Blood. 2016 April 7;127(14):1743. PMCID: PMC4825412.

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Regulation of the genetic code in megakaryocytes and platelets. Rondina MT, Weyrich AS. J Thromb Haemost. 2015 June; 13 Suppl 1(0 1):S26. PMCID: PMC4498409.

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The platelet transcriptome in health and disease. Rowley JW, Weyrich AS, Bray PF. AD Michelson, ed. In Platelets Fourth Edition Elsevier London. 2019:139. 

U of U Health Key Faculty Collaborators

Guy A. Zimmerman, MD 
Matthew T. Rondina, MD
Jesse Rowley, PhD