Two different systems are studied in my laboratory: (1) regulation of histone mRNA metabolism in mammalian cells and (2) regulation of snRNA metabolism in sea urchin embryos. Histone genes are the only class of genes which lack introns and which lack polyA. Histone mRNA levels are tightly regulated during the cell cycle coordinately with DNA synthesis. Many chemotherapy drugs (e.g. methotrexate, cytosine arabinoside) have a rapid direct effect on histone mRNA metabolism, blocking DNA replication and minicking the changes that occur at the end of DNA replication. Much of the regulation of histone mRNA is postranscriptional and is mediated through the conserved stem-loop structure at the 3' end of all histone mRNAs. Both the nuclear processing of the pre-histone mRNA and the cytoplasmic stability of the histone mRNA are regulated. Currently, we are focusing on the role of proteins which bind the stem-loop in the nucleus and cytoplasm. We are also trying to understand the signaling system which couples DNA replication to histone mRNA stability in the cytoplasm.

Sea urchin embryos develop from an egg to a fully differentiated larva in four days. We are studying the changes in small nuclear RNAs, molecules required for pre-mRNA processing, which occur during early embryogenesis. There are two sets of genes for snRNAs; a tandemly repeated set expressed only early in embryogenesis and a single-copy set expressed late in embryogenesis. Expression of the genes is studies using in vitro transcription and by microinjection of genes into sea urchin embryos. Currently, we are focusing on purifying and cloning the factors involved in temporal regulation.