• Primary Faculty Profiles
• Bankert, Richard, Ph.D., V.M.D., Professor
• Bianco, Piero, Ph.D., Associate Professor
• Campagnari, Anthony, Ph.D., Professor
• Collins, Arlene, Ph.D., Associate Professor
• Connell, Terry, Ph.D., Professor
• Egilmez, Nejat, Ph.D., Associate Professor
• Hakansson, Anders, Ph.D., Assistant Professor
• Hay, John, Ph.D., Professor
• Jacobs, Amy, Ph.D., Assistant Professor
• Melendy, Thomas, Ph.D., Associate Professor
• Panepinto, John, Ph.D., Assistant Professor
• Read, Laurie, Ph.D., Professor
• Russell, Michael, Ph.D., Professor
• Ruyechan, William, Ph.D., Professor and Chairman
• Thacore, Harshad, Ph.D., Associate Professor
• Williams, Noreen, Ph.D., Professor
• Adjunct Faculty Profiles
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Education:

1990-1994, Postdoc, Seattle Biomedical Research Institue
1990, Ph.D., Tufts University School of Medicine, Boston, MA
1985, M.A., University of California, Santa Barbara
1982, Bachelor of Arts, Boston University, Boston, MA

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Research Interests:

Posttranscriptional Regulation of Gene Expression in Parasitic Protozoa

In our laboratory, we study the eukaryotic parasite, Trypanosoma brucei, which is the causative agent of human African trypanosomiasis.  Essential and novel processes in this parasite may serve as starting platforms for new drug therapies.  In addition to being of great medical and economic importance, T. brucei is also an excellent model system for the study of posttranscriptional gene regulation, because regulation at the level of transcription is essentially absent in this organism.  The primary focus of our laboratory is on the mechanisms and regulation of two RNA processing events in T. brucei:  RNA editing and RNA turnover.  A third related area of research is the mechanism by which posttranslational modification of RNA binding proteins by arginine methylation modulates RNA processing, stability, and translation.

RNA editing: 
RNA editing is a novel mechanism for regulating gene expression in which sequence information is added to mRNAs after transcription by specific insertion and deletion of uridine residues.   Editing generates translatable messages by creating the open reading frames as well as proper initiation and termination signals.  The phenomenon is of fundamental importance in understanding how genetic information can be stored and processed, and it is an essential process in trypanosomes.  We identified RNA binding proteins that act as RNA editing accessory factors, and which are required for the editing of specific RNAs or classes of RNAs.  We are currently determining the molecular mechanisms by which these proteins modulate RNA-RNA, RNA-protein, and protein-protein interactions to facilitate the editing process using a combined genetic and biochemical approach.

RNA turnover:
The levels of translatable mRNAs are dictated by the balance between transcription rates and mRNA decay rates.  The decay rates of specific RNAs are determined by both cis-acting sequences within the mRNA itself as well as trans-acting proteins that interact with those RNA sequences.  We have developed an in vitro RNA turnover system for identification of cis- and trans-acting factors that modulate RNA decay rates.  We identified small edited RNA sequences that dramatically affect the rate of RNA decay, and showed that 3’ poly(A) tails differentially affect the decay rate of an RNA depending on its editing status. We are using also our in vitro system as a starting point for biochemical purification of the proteins that catalyze and regulate RNA turnover pathways.  In addition, we use a bioinformatics approach to identify trypanosome proteins involved in RNA turnover.  Ultimately, we use genetic studies in trypanosomes to determine the roles of these proteins in the turnover of the various classes of mitochondrial RNAs. 

Protein arginine methylation: 
Methylation of arginine residues in proteins is a posttranslational modification whose importance in areas such as signal transduction, RNA trafficking, RNA processing, and transcription has recently become apparent.  Interestingly, a very large percentage of proteins that undergo arginine methylation are RNA binding proteins.  Studies are currently underway to determine the roles of arginine methylation of RNA binding proteins in posttranscriptional gene regulatory processes in T. brucei.

See also http://www.smbs.buffalo.edu/wcmpi/Faculty/read.html

Relevant references:

Fisk, J.C, M.L. Ammerman, V. Presnyak, and L.K. Read. 2008. TbRGG2, an essential RNA editing accessory factor in two Trypanosoma brucei life cycle stages. J. Biol. Chem. In press.

Ammerman, M.L., J.C. Fisk, and L.K. Read. 2008. gRNA/pre-mRNA annealing and RNA chaperone activities of RBP16. RNA 14:1069-1080.

Mattiacio, J.L. and L.K. Read. 2008. Roles for TbDSS-1 in RNA surveillance and decay of maturation by-products from the 12S rRNA locus. Nucl. Acids Res. 36:319-329.

Goulah, C.C. and L.K. Read. 2007. Differential effects of RBP16 arginine methylation on mRNA binding, gRNA binding, and gRNP formation. J. Biol. Chem. 282:7181-7190.

Pasternack, D.A., J. Sayegh, S. Clarke, and L.K. Read. 2007. Evolutionarily divergent type II protein arginine methyltransferase in Trypanosoma brucei.  Eukaryot. Cell 6:1655-1681.

Kao, C-Y. and L.K. Read. 2005. Opposing effects of polyadenylation on the stability of edited and unedited mitochondrial RNAs in Trypanosoma brucei. Mol. Cell. Biol. 25:1634-1644.