Enzymes that metabolize RNA (ribonucleases, or RNases) play fundamental, primal roles in the living cell. If these ribonucleases malfunction, then mis-transcribed, mis-processed, mis-metabolized, or mis-sorted RNAs can have a severe impact on normal cellular function. Because all cellular RNAs are potential substrates for RNases, and RNAs are omnipresent and multi-functional, local or global RNA defects can be an etiological agent of diseases and/or contribute to disease progression.
My group has been asking two broad questions: How does the spatiotemporal control of RNase interactions and post-translational modifications relate to RNase recognition and metabolism of specific classes of RNAs in living cells? How does RNase activity relate to cell structure and function? To answer these questions, we are studying Dis3, Rrp6, and the ribonucleometabolic exosome. Dis3 is a processive, sequence-nonspecific 3' to 5' RNase that is homologous to eubacterial RNase R/II. Rrp6 is a distributive, sequence-nonspecific 3' to 5' RNase similar to eubacterial RNase D. The exosome is a multi-subunit complex or set of complexes that contain(s) putative RNases (Rrp41, Rrp42, Rrp43, Rrp45, Rrp46, Mtr3 are eukaryotic homologs of the eubacterial RNase PH) and the S1 RNA-binding domain proteins Rrp4, Rrp40, and Csl4. We have proposed and are testing the hypothesis that these subunits assemble into multiple independent, functionally interrelated complexes called exozymes. Extending upon this RNA research, I recently compiled an incommensurable, trans-disciplinary, neologistical, axiomatic theory of life from quantum gravity to the living cell.
We are currently using two model organisms (Drosophila melanogaster, Saccharomyces cerevisiae) and several approaches (cell biology, molecular biology, genetics, transcriptomics, bioinformatics, biochemistry) to test the hypothesis and theory.
Hou, D., Ruiz, M., and E. D. Andrulis (2012) The ribonuclease Dis3 is an essential regulator of the developmental transcriptome. BMC Genomics, 13:359. [E-pub]
Kiss, D. L., Hou, D., Gross, R. H., and E. D. Andrulis (2012) Dis3- and exosome subunit-responsive 3' mRNA instability elements. Biochemical and Biophysical Research Communications, 423: 461-66. [PubMed]
Andrulis, E.D. (2012) Theory of the Origin, Evolution, and Nature of Life. Life 2(1):1-105 [E-Pub]
Smith S. B., Kiss D. L., Turk E., Tartakoff, A. M., E.D. Andrulis (2011) Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant. Yeast, 28(11):755-69. [PubMed]
Kiss, D. L. and E. D. Andrulis (2011) The exozyme model: a continuum of functionally distinct complexes. RNA, 17(1):1-13. [PubMed]
Mamolen, M., Davis, S. M., and E. D. Andrulis (2010) Drosophila melanogaster Dis3 N-terminal domains are required for ribonuclease activities, nuclear localization, and exosome interactions. Nucleic Acids Research, 38(16):5507-17. [PubMed]
Kiss, D.L. and E. D. Andrulis (2010) Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits. RNA, 16(4):781-91. [PubMed]
Mamolen, M. and E. D. Andrulis (2009) Characterization of the Drosophila melanogaster Dis3 ribonuclease. Biochemical and Biophysical Research Communications, 390: 529-34. [PubMed]