Is RNA in Serum Bound to Nucleoprotein Complexes?

DNA and RNA are present in normal and diseased human plasma (1)(2)(3)(4)(5)(6)(7) and in the extracellular media of eukaryotic cell cultures (8)(9). Two excellent recent reviews (10)(11) indicated that neither necrotic nor apoptotic cells may fully explain the presence of DNA in plasma. In favor of apoptosis is the finding of a DNA ladder pattern after electrophoresis. Electrophoresis of nick-translated DNA isolated from plasma of healthy controls produced autoradiographic bands at sizes equivalent to whole-number multiples (1–5×) of nucleosomal DNA (185–200 bp) (12). Nevertheless, DNA is released in a homeostatic fashion (8)(9), and newly synthesized DNA is preferentially released (9)(13)(14), suggesting that neither apoptosis nor necrosis is the sole source of this DNA. Cells not only release DNA but have specialized receptors for these nucleoprotein complexes as well. A recent study (15) showed that nucleosomes bind to the exterior of cultured mesangial cells in a receptor-mediated fashion. Competition studies demonstrated inhibition of binding by nucleosomes, 200/400-bp DNA, salmon sperm DNA, and, to a lesser extent, single-stranded DNA. DNase treatment removed 95.3% ± 2.3% of the cell-associated radioactivity at 37 °C. The authors view this as “essentially all cell-associated radioactivity”, although a small percentage remained (2.4–7.0%) along with some remaining nuclear labeling by autoradiography, suggesting the possibility of uptake of labeled oligonucleosomes.