Many molecular processes in the cytoplasm take place in or on subcellular organelles, such as the mitochondria, Golgi vesicles, and endoplasmic reticulum. The same is probably true for the nucleus, although, except for the chromosomes and nucleoli, subnuclear organelles have been poorly defined. Our studies concern the role of nuclear organelles in the synthesis and processing of RNA.

We are concentrating on a structure in the nucleus called the Cajal body, so named because it was first described 100 years ago by the Spanish neurobiologist and Nobel laureate Ramon y Cajal. Until recently very little was known about the Cajal body, but modern microscopical techniques, particularly immunofluorescent staining, in situ hybridization, labeling of proteins with green fluorescent protein, and confocal microscopy have brought rapid progress. We now know that Cajal bodies contain many factors involved in transcribing and modifying both pre-messenger RNA and pre-ribosomal RNA. Since neither of these processes itself takes place in the Cajal body, we think that the Cajal body is a site for assembly of factors required for transcription and RNA processing.

We study the Cajal body in tissue culture cells, in frog oocytes, and in the fly Drosophila. The frog oocyte contains a giant nucleus called the germinal vesicle or GV, whose large size makes it ideal for both biochemical and cell biological studies. It contains the so-called lampbrush chromosomes, giant structures in which actively transcribing genes are visible by conventional light microscopy. A GV also contains over 1000 nucleoli and 50-100 Cajal bodies. The Cajal bodies are many times larger in the GV than in somatic nuclei, permitting a variety of biochemical and biophysical measurements that otherwise would be impossible. Although Drosophila cells are much smaller than frog cells, flies have the great advantage that they permit genetic studies on Cajal body components. In Drosophila one can manipulate the genes that encode proteins and RNAs of the Cajal body, and follow the consequences in various embryonic, larval, and adult tissues.

The general lesson from our studies is that complex molecular events in the nucleus, like those in the cytoplasm, occur in or on organelles that are large enough to study by conventional light microscopy. Exactly where these events take place and how the structure of the nucleus contributes to their regulation are important aspects of nuclear physiology.