Professor, Department of Molecular & Cell Biology
72 East Concord Street, Evans, Room 426
Boston, MA 02118
PhD, Institute of Molecular Biology, Russian Academy of Sciences, 1995
Post-doctoral training, Howard Hughes Medical Institute, University of California, Los Angeles, 1996-2000
Molecular mechanisms of RNA processing in Trypanosomes
Trypanosomatids are protozoan hemoflagellates responsible for a variety of neglected human diseases including Chagas’ disease, leishmaniasis and African sleeping sickness. These protists represent one of the earliest mitochondria-containing branches of the eukaryotic lineage and possess many unusual biological processes such as antigenic variation, multi-cistronic Pol II transcription, trans-splicing and mitochondrial RNA editing. Our research efforts concentrate on RNA processing in African trypanosomes. The main goal of the “mitochondria-centered” program is to understand how genetic information is transferred between RNA molecules during U-insertion/deletion editing. Molecular mechanisms of U-insertion/deletion mRNA editing, polyadenylation, translation and decay, and guide RNA biogenesis are investigated by biochemical, genetic, structural and proteomic approaches. We also explore biological roles of non-canonical poly(A) polymerases (ncPAPs) and terminal RNA uridylyl transferases (TUTases) in Trypanosomes. Life without transcriptional control practiced by these parasites stimulates us to look at the alternative, RNA decay-based pathways regulating expression of their nuclear genome. Crystallographic studies of substrate recognition by TUTases and ncPAPs provide a foundation for rational design of trypanocides. Exciting projects are available for highly-motivated graduate and post-doctoral researchers in our state-of-the-art, NIH-funded laboratory.
Currently active projects
1. Cellular functions of RNA uridylation
2. Polyadenylation of mitochondrial mRNAs
3. Guide RNA biogenesis and function
4. Nuclear non-canonical poly(A) polymerases and mRNA decay
5. NTP Selectivity of template-independent transferases
6. Structure-function of the RNA editing core complex
7. Structure-function of the guide RNA binding complex
1. Aphasizheva,I., Maslov,D., Wang,X., Huang,L. and Aphasizhev,R. (2011) Pentatricopeptide Repeat Proteins Stimulate mRNA Adenylation/Uridylation to Activate Mitochondrial Translation in Trypanosomes. Mol. Cell, 42, 106-117. (Issue Highlights, Preview by Read et al. Research Highlights, Nature Structural and Molecular Biology).
2. Stagno,J., Aphasizheva,I., Bruystens,J., Luecke,H. and Aphasizhev,R. (2010) Structure of the mitochondrial editosome-like complex associated TUTase 1 reveals divergent mechanisms of UTP selection and domain organization. J. Mol Biol., 399, 464-475.
3. Ringpis,G.E., Aphasizheva,I., Wang,X., Huang,L., Lathrop,R.H., Hatfield,G.W. and Aphasizhev,R. (2010) Mechanism of U Insertion RNA Editing in Trypanosome Mitochondria: The Bimodal TUTase Activity of the Core Complex. J. Mol. Biol., 399, 680-695.
4. Ringpis,G.E., Stagno,J. and Aphasizhev,R. (2010) Mechanism of U-insertion RNA Editing in Trypanosome Mitochondria: Characterization of RET2 Functional Domains by Mutational Analysis. J. Mol Biol., 399, 696-706.
5. Aphasizheva,I. and Aphasizhev,R. (2010) RET1-catalyzed Uridylylation Shapes the Mitochondrial Transcriptome in Trypanosoma brucei. Mol. Cell. Biol., 30, 1555-1567.
6. Aphasizheva,I., Ringpis,G.E., Weng,J., Gershon,P.D., Lathrop,R.H. and Aphasizhev,R. (2009) Novel TUTase associates with an editosome-like complex in mitochondria of Trypanosoma brucei. RNA, 15, 1322-1337.
7. Weng,J., Aphasizheva,I., Etheridge,R.D., Huang,L., Wang,X., Falick,A.M. and Aphasizhev,R. (2008) Guide RNA-Binding Complex from Mitochondria of Trypanosomatids. Mol. Cell, 32, 198-209.
8. Etheridge,R.D., Aphasizheva,I., Gershon,P.D. and Aphasizhev,R. (2008) 3′ adenylation determines mRNA abundance and monitors completion of RNA editing in T. brucei mitochondria. EMBO J., 27, 1596-1608.
9. Stagno,J., Aphasizheva,I., Aphasizhev,R. and Luecke,H. (2007) Dual Role of the RNA Substrate in Selectivity and Catalysis by Terminal Uridylyl Transferases. Proc. Natl. Acad. Sci. U S A., 104, 14634-14639.
10. Stagno,J., Aphasizheva,I., Rosengarth,A., Luecke,H. and Aphasizhev,R. (2007) UTP-bound and Apo structures of a minimal RNA uridylyltransferase. J. Mol. Biol., 366, 882-899.
Structures and functions of RNA editing TUTases. R01AI091914. PI: R. Aphasizhev; NIH/NIAID; 2010-2015.
Guide RNA binding complex. R01AI101057. PI: R. Aphasizhev; NIH/NIAID; 2012-2017.