Mark Schmitt, PhD
Professor of Biochemistry and Molecular Biology
Interim Vice President for Research
Dean, College of Graduate Studies
RESEARCH PROGRAMS AND AFFILIATIONS
Biochemistry and Molecular Biology
Biomedical Sciences Program
Cancer Research Program
Ribonucleoprotein assembly and biogenesis; mitochondrial RNA import, mRNA degradation, cell cycle control
Postdoctoral Fellow: Stanford University
PhD: Dartmouth Medical School, 1990
RESEARCH ABSTRACTThe main goal of our research is to determine the function and regulation of the ribonucleoprotein endoribonuclease, RNase MRP, in the cell division cycle in late telophase. The incorrect regulation of cell division is the basis of all cancers. Understanding the details of how cell division is regulated and controlled is essential for controlling cancer and finding cures. Previous work had found that RNase MRP is directly involved in the late stages of the cell division cycle by regulating the activity of the cyclin dependent kinase. Cells that are defective in RNase MRP have a delayed telophase. We have made extensive progress in identifying the exact molecular mechanism of this regulation. We have found that at a particular time in the cell division cycle the RNase MRP enzyme is released from the nucleus a compartment in the cell where it is kept sequestered. The release of this endoribonuclease allows it to breakdown specific mRNAs for B-type cyclins that are required for the activity of the cyclin dependent kinase, the promotes inactivation of the cyclin dependent kinase and the termination of the cell cycle. These studies have also led us to discovering a new organelle, the TAM (Temporal Asymmetric MRP) body. We have found that this structure is P (processing) body "like". But in contrast to P bodies that are found throughout cells and the cell cycle, TAM bodies are temporally and spatially assembled organelles whose function is to degrade specific mRNAs at a discrete time and location in the cell cycle. RNase MRP localizes to this organelle during mitosis and it is in this location that the B-cyclin mRNAs are degraded.
RNase MRP is conserved throughout eukaryotes and mutations in the human RNA component have implicated this enzyme as an essential growth regulator. Human mutations cause Cartilage Hair Hypoplasia (CHH) a recessively inherited disorder characterized by short stature, brittle hair, anemia, immunodeficiency, and a predisposition to the development of lymphomas and other cancers. Data from our lab in collaboration with others has shown that human RNase MRP is also playing a role in destabilizing certain mRNAs. Failure to normally degrade certain mRNAs could easily cause the cell cycle delay seen in the human disease and the resulting phenotypes. Hence, these studies will have direct implications on human disease and pathogenesis.
Esakova O, Perederina A, Quan C, Schmitt ME, Krasilnikov AS. Footprinting analysis demonstrates extensive similarity between eukaryotic RNase P and RNase MRP holoenzymes. RNA. 2008 Aug;14(8):1558-67. Epub 2008 Jun 25.
Perederina A, Esakova O, Koc H, Schmitt ME, Krasilnikov AS. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs. RNA. 2007 Oct;13(10):1648-55. Epub 2007 Aug 23.
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