Department of Molecular Biology and Biochemistry
Waksman Institute, Busch Campus
Piscataway, NJ 08854
Stem cells, hematopoiesis,and epigenetic control of chromatin integrity in Drosophila
We are studying the mechanisms controlling RNA processing (i.e. translation, localization, and stability)of specific sets of transcripts. We have identified and characterized a novel highly conserved gene, Zfrp8/PDCD2 and shown that it is essential in stem cells in flies, mouse and human and is also required for growth of cancer cells. Recently, we discovered that it is required for the nuclear export of select mRNAs and TE transcripts. It also interacts with the small ribosomal subunit and complexes with mRNA binding proteins. Our data suggest that Zfrp8/PDCD2 controls subcellular localization of select RNAs and the association of mRNA-RNP with ribosomes.
We also have identified Tet/TET1 as a new Zfrp8/PDCD2 interacting protein. In vertebrates, TET proteins function in DNA demethylation converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), modifications that are not detected in Drosophila DNA. A recent study shows that vertebrate Tet proteins can also convert 5mrC to 5hmrC in RNA. Inspired by this discovery we have shown that 5hmrC also exists in flies and depends on Tet activity. We hypothesize that Tet modifies specific transcripts and regulates the recruitment of Zfrp8 to these RNAs, thereby controlling their processing and translation. Our current work is aimed at elucidating how the two genes function with each other and what steps in RBA processing they control.