Harold Charles Smith, Ph.D.

See information for Patients. Viewing information for Researchers.

Normal and cancer cells express more diversity in proteins than can be accounted for by the predicted number of expressed genomic DNA sequence. Expansion of the genomically encoded expressed sequences through alternative processing of RNA, such as mRNA editing, is a logical hypothesis for how protein diversity and variations seen as tissue-specific and regulated expression of proteins can be achieved. The specific focus of the research is to identify and characterize novel mammalian mRNA editing systems that employ a zinc-dependent deamination mechanism for the post-transcriptional conversion of cytidine to uridine at select sites within mRNAs. Computational modeling has suggested a family of mammalian enzymes known as Cytidine Deaminases Active on RNA or CDARs as responsible for C to U editing of mRNAs.

The expression of these enzymes in biology suggests that mRNA editing may be involved in numerous physiological processes and could be manipulated for the prevention of cardiovascular disease, HIV infection and cancer, and is also necessary for production of antibodies in B lymphocytes. Recent evidence indicates that the enzyme involved in suppressing HIV-1 infectivity (CEM15) and the enzyme that promotes antibody production (AID) may act to mutate deoxy cytidine in DNA rather than or in addition to RNA.

Our research involves molecular biology and protein techniques, DNA microarray analyses and computational biology to identify the mRNAs that are edited by CDARs and to determine the biological consequence of these editing events in terms of the predicted changes in the types of protein structures and functions that can be expressed. Our studies have demonstrated how cytidine to uridine mRNA editing contributes to expansion in the diversity of expressed mRNA sequences known collectively as the transcriptome.

We are also evaluating the regulatory mechanisms controlling the expression of editing factors and their localization in the cell nucleus. The development of this new information will establish an important new annotation of the human genome that will serve as a frame of reference for studies of proteins involved in health and disease and mechanisms regulating their expression.

Current Appointments

• Professor - Department of Biochemistry and Biophysics (SMD)

Education
PhD Molecular Biology	St Univ at Buffalo	1982
MA Molecular Biology	St Univ at Buffalo	1980
MS Veterinary Medicine	Purdue University	1978
BS Biology	Purdue University	1975

Lab Website

http://dbb.urmc.rochester.edu/labs/smith/

---

Recent Journal Articles
Showing the 5 most recent journal articles. (74 available)
Salter JD; Krucinska J; Raina J; Smith HC; Wedekind JE. "A Hydrodynamic Analysis of APOBEC3G Reveals a Monomer-Dimer-Tetramer Self-Association That Has Implications for Anti-HIV Function." Biochemistry. 2009; Epub 2009 Oct 22.
Smith, H. C.;. "RNA and DNA Editing: Molecular Mechanisms and Their Integration into Biological Systems". (H.C. Smith, ed) 16 chapters, Wiley Press, NY, 2008. (2008).
Bennett, R. P.; Presnyak, V.; Wedekind, J. E.; Smith, H. C.;. "Nuclear Exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA binding". J Biol Chem 283 (2008): 7320-7.
Bennett, R. P.; Salter, J. D.; Liu, X.; Wedekind, J. E.; Smith, H. C.;. "APOBEC3G Subunits Self-associate via the C-terminal Deaminase Domain". J Biol Chem 283 (2008): 33329-36.
Jin, X.; Wu, H.; Smith, H.C.;. "APOBEC3G levels predict rates of progression to AIDS". Retrovirology 4 (2007): 20-7.