Scientists long have thought the transformation of pre-mRNA into mature mRNA--called splicing--happens only in a cell's nucleus. But using stem cells from human umbilical cord blood to engineer the precursor cell that forms platelets and platelets isolated from the blood of study subjects, the Utah researchers found that splicing also takes place in the cytoplasm of circulating platelets.
The U researchers, who report their findings in the Aug. 12 edition of Cell, also identified the pre-mRNA in blood platelets that codes for Interleukin 1 (IL-1), a key protein in an ancient molecular system that plays major roles in inflammation, defense against infection, organ development, and disease. When blood platelets are activated through biochemical signals in response to injury, the IL-1 pre-mRNA is processed into the mature mRNA and then directs production of the critical inflammatory protein.
Finding that platelets can splice the IL-1 pre-mRNA was completely unexpected and emerged while the researchers were engaged in earlier studies of how platelets communicate with certain leukocytes (white blood cells). During that investigation they found evidence of platelets making new proteins, which led them to pursue the mechanisms that are involved, said Guy A. Zimmerman, M.D., professor of internal medicine and one of the study's co-authors.
"The idea that blood platelets could make proteins without having a nucleus had been thought heretical," said Zimmerman, who also heads the U's Program in Human Molecular Biology and Genetics at the Eccles Institute of Human Genetics. "To find that splicing takes place outside the nucleus has potential implicati