Denis et al. made the unexpected discovery that precursor mRNAs (pre-mRNAs) and functional spliceosomes are found in the cytoplasm of platelets and, further, that splicing of this cytoplasmic pre-RNA is regulated by signals deriving from platelet activation. In nucleated cells, noncoding introns are removed from newly transcribed pre-mRNA by the spliceosome (a nuclear complex containing small nuclear ribonucleoproteins and auxiliary proteins), creating translatable mRNA, which may then be exported from the nucleus. Thus, one would not expect that platelets, anucleate blood cells that bud from megakaryocytes, would contain spliceosome components or pre-mRNAs. Denis et al. found, however, that components of the spliceosome (both proteins and small nuclear splicing RNAs) were present not only in the cytoplasm of human megakaryocytes but also in circulating platelets. Interleukin-1β (IL-1β) pre-mRNA was present in the cytoplasm of quiescent platelets (and in the cytoplasm of megakaryocytes extending the proplatelets that give rise to platelets), whereas platelets activated by adhesion to fibrinogen in the presence of thrombin contained mature IL-1β mRNA and protein. Indeed, reverse transcription polymerase chain reaction (RT-PCR) revealed a time-dependent decrease in IL-1β pre-mRNA and an increase in IL-1β mRNA after platelet activation. Moreover, IL-1β pre-mRNA that was transcribed in vitro was spliced into mRNA by a fraction of platelet extract. Thus, pre-mRNA splicing not only takes place in the cytoplasm of platelets but also provides a mechanism for regulating cytokine production after platelet activation. Meshorer and Misteli provide context in a Preview and speculate on the possibility that pre-mRNA splicing could occur in the cytoplasm of other cell types.
M. M. Denis, N. D. Tolley, M. Bunting, H. Schwertz, H. Jiang, S. Lindemann, C. C. Yost, F. J. Rubner, K. H. Albertine, K. J. Swoboda, C. M. Fratto, E. Tolley, L. W. Kraiss, T. M. McIntyre, G. A. Zimmerman, A. S. Weyrich, Escaping the nuclear confines: Signal-dependent pre-mRNA splicing in anucleate platelets. Cell 122, 379-391 (2005). [PubMed]
E. Meshorer, T. Misteli, Splicing misplaced. Cell 122, 317-318 (2005). [PubMed]