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Harold C. Smith, Ph.D.

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Office: (585) 275-4267

Fax: (585) 275-6007

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Lab: (585) 275-1882

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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.



BS | Purdue University

MS | Purdue University
Veterinary Medicine

MA | St Univ at Buffalo
Molecular Biology

PhD | St Univ at Buffalo
Molecular Biology


Journal Articles

Smith HC. "RNA binding to APOBEC deaminases; Not simply a substrate for C to U editing." RNA biology.. 2017 Sep 2; 14(9):1153-1165. Epub 2016 Nov 21.

Polevoda B, Joseph R, Friedman AE, Bennett RP, Greiner R, De Zoysa T, Stewart RA, Smith HC. "DNA mutagenic activity and capacity for HIV-1 restriction of the cytidine deaminase APOBEC3G depend on whether DNA or RNA binds to tyrosine 315." The Journal of biological chemistry.. 2017 292(21):8642-8656. Epub 2017 Apr 05.

Hilimire TA, Chamberlain JM, Anokhina V, Bennett RP, Swart O, Myers JR, Ashton JM, Stewart RA, Featherston AL, Gates K, Helms ED, Smith HC, Dewhurst S, Miller BL. "HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells." ACS chemical biology.. 2017 12(6):1674-1682. Epub 2017 May 05.

Books & Chapters

Book Title: RNA and DNA Editing: Mechanisms and Their Impact on Biological Systems
Author List: J. Cruz-Reyes, J.D. Alfonzo, T. Meier, S. Maxwell, C. McElrevey, J.E. Wedekind, G.L. Verdine, B. Brown, E. Esinberg, S. Mass,, S. Lin, Y.-T. Yu, V. Blanc, N.O Davidson, M. Ohman, R. Harris, A.M. Sheehy, G. Carmichael
Published By: Wiley & Sons2008

Chapter Title: Determination of C to U Editing Activity in Cells and Biochemical Isolates
Book Title: methods in Enzymology
Author List: Smtih, Harold, C.
Edited By: Gott, J
Published By: Academic Press2007

Chapter Title: Editing Informational Content of Expressed DNA Sequences and Their Transcripts
Book Title: The Implicit Genome
Author List: Smith, Harold, C.
Edited By: Caporale, L.
Published By: Oxford University Press2006