Clinton C. MacDonald, Ph.D. | Texas Tech University Health Sciences Center

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Clinton C. MacDonald, Ph.D.

Professor

Clinton C. MacDonald, Ph.D.
 

Ph.D. Molecular Biology and Biochemistry
State University of New York at Stony Brook
Curriculum Vitae
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Lubbock, TX 79430-6540
Office Phone: (806) 743-2524
clint.macdonald@ttuhsc.edu

Research Interests

Tissue-specific mechanisms of mRNA processing, polyadenylation, control of RNA processing during spermatogenesis and brain development.

Current Projects

Role of 蟿CstF-64 (gene symbol Cstf2t) in polyadenylation of germ cell mRNAs.
Mechanisms of polyadenylation are different in male germ cells, and we investigate the consequences of those differences. One of those differences is that testes express a variant form of the CstF-64 polyadenylation protein that we named 蟿CstF-64 (Cstf2t). We have found that male Cstf2t knockout mice are infertile due to incorrect expression of key spermatogenesis genes including intronless small genes and LINE repetitive elements. Current projects are to determine how 蟿CstF-64 controls polyadenylation of those mRNAs.

Role of CstF-64 splice variants in brain function.
There is a spliced variant of CstF-64 that is expressed only in neurons, which introduces a new domain in CstF-64. We call this spliced variant 脽CstF-64. We are trying to determine the how this variant functions in brains and why it is important.

The functions of CstF-64 in control of polyadenylation.
Discovered in 1988, CstF-64 has been shown to be the central regulatory protein in polyadenylation. Despite its importance, many of its functions remain mysteries. We have developed several assays for CstF-64 and are using them to test functions of its individual domains.

Selected Publications

  • Grozdanov, P. N., Amatullah, A., Graber, J. H., and MacDonald, C. C. (2016). 鈥溝凜stF-64 mediates correct mRNA polyadenylation and splicing of activator and repressor isoforms of the cyclic AMP-responsive element modulator (CREM) in mouse testis.鈥� Biology of Reproduction, in the press.
  • Grozdanov, P. N. and MacDonald, C. C. (2015) 鈥淕eneration of plasmid vectors expressing FLAG-tagged proteins under the regulation of human elongation factor鈥�1伪 promoter using the Gibson assembly cloning.鈥� J. Visual. Exp. in the press (doi: 10.3791/52235).
  • Youngblood, B. A. and MacDonald, C. C. (2014) 鈥淐stF鈥�64 is necessary for endoderm differentiation resulting in cardiomyocyte defects.鈥� Stem Cell Res. 13(3A), 413鈥�421 (doi: 10.1016/j.scr.2014.09.005).
  • Youngblood, B. A., Grozdanov, P. N., and MacDonald, C. C. (2014) 鈥淐stF鈥�64 supports pluripotency and cell cycle progression in embryonic stem cells through histone 3鈥� end processing.鈥� Nucl. Acids Res. 42(13), 8330鈥�8342 (doi: 10.1093/nar/gku551).
  • Alfano, R., Youngblood, B. A., Zhang, D., Huang, N., and MacDonald, C. C. (2014) 鈥淗uman Leukemia Inhibitory Factor produced by the ExpressTec method from rice (Oryza sativa L.) is active in human neural stem cells and mouse induced pluripotent stem cells,鈥� Bioengineered 5(3), 180鈥�185 (doi: 10.4161/bioe.28996).
  • Youngblood, B. A., Alfano, R., Pettit, S., Zhang, D., Dallmann, H. G., Huang, N., and MacDonald, C. C. (2014) 鈥淎pplication of recombinant human Leukemia Inhibitory Factor (LIF) produced in rice (Oryza sativa L.) for maintenance of mouse embryonic stem cells.鈥� J. Biotechnol. 172, 67鈥�72 (doi: 10.1016/j.jbiotec.2013.12.012).
  • Grozdanov, P. N. and MacDonald, C. C. (2014) 鈥淗igh-throughput Sequencing of RNA isolated by Crosslinking and Immunoprecipitation (HITS-CLIP) to determine sites of binding of CstF鈥�64 on nascent RNAs.鈥� Methods in Molecular Biology 1125, 187鈥�208 (doi: 10.1007/978鈥�1鈥�62703鈥�971鈥�0_17).
  • Hockert, J. A. and MacDonald, C. C. (2014) 鈥淭he Stem-Loop Luciferase Assay for Polyadenylation (SLAP) method for determining CstF鈥�64-dependent polyadenylation activity.鈥� Methods in Molecular Biology 1125, 109鈥�117 (doi: 10.1007/978鈥�1鈥�62703鈥�971鈥�0_9).
  • Shankarling, G. S. and MacDonald, C. C. (2013) 鈥淧olyadenylation site-specific differences in the activity of the neuronal 尾CstF鈥�64 protein in PC鈥�12 cells.鈥� Gene 529, 220鈥�227 (doi: 10.1016/j.gene.2013.08.007).
  • Li, W., Yeh, Hsiang-Jui, Shankarling, G. S., Tian, B., and MacDonald, C. C. (2012) 鈥淭he 蟿CstF鈥�64 polyadenylation protein controls genome expression in testis.鈥� PLoS ONE 7, e48373 (doi: 10.1371/journal.pone.0048373).
  • Hockert, K. J., Martincic, K., Mendis-Handagama, S. M. L. C., Borghesi, L. A., Milcarek, C., Dass, B., and MacDonald, C. C. (2011) 鈥淪permatogenic but not immunologic defects in mice lacking the 蟿CstF-64 polyadenylation protein,鈥� Journal of Reproductive Immunology, 89, 26鈥�37 (doi: 10.1016/j.jri.2011.01.018).
  • Tardif, S., Akrofi, A., Dass, B., Hardy, D. M., and MacDonald, C. C. (2010) 鈥淚nfertility with impaired zona pellucida adhesion of spermatozoa from mice lacking 蟿CstF-64.鈥� Biology of Reproduction 83, 464鈥�472.
  • MacDonald, C. C. and McMahon, K. W. (2010) 鈥淭issue-Specific Mechanisms of Alternative Polyadenylation: Testis, Brain and Beyond,鈥� WIREs RNA 1, 494鈥�501
  • Hockert, J. A., Yeh, H-J. and MacDonald, C. C. (2010). 鈥淭he hinge domain of the cleavage stimulation factor protein CstF-64 is essential for CstF-77 interaction, nuclear localization, and polyadenylation,鈥� J. Biol. Chem., 285, 695鈥�704. This manuscript was chosen as Paper of the Week by the Editors of the Journal of Biological Chemistry.
  • Shankarling, G., Coates, P. W., Dass, B., and MacDonald, C. C. (2009) 鈥淎 family of splice variants of CstF-64 expressed in vertebrate nervous systems,鈥� BMC Molecular Biology 10, 22.
  • Dass, B., Tardif, S., Park, J-Y., Tian, B., Weitlauf, H. M., Hess, R. A., Carnes, K., Griswold, M. D., Small, C. L., and MacDonald, C. C. (2007). 鈥淟oss of polyadenylation protein 蟿CstF-64 causes spermatogenic defects and male infertility.鈥� Proc. Natl. Acad. Sci., USA 104, 20374鈥�20379.
  • Liu, D., Brockman, J. M., Dass, B., Hutchins, L. N., McCarrey, J. R., MacDonald, C. C., Singh, P., and Graber, J. H. (2007). 鈥淪ystematic variation in mRNA 3鈥�-processing signals during mouse spermatogenesis.鈥� Nucleic Acids Research 35, 234鈥�246.
  • Monarez, R. R., MacDonald, C. C., and Dass, B. (2007). 鈥淧olyadenylation Proteins CstF-64 and 蟿CstF-64 Exhibit Differential Binding Affinities for RNA Polymers.鈥� Biochemical J. 401, 651鈥�658.
  • McMahon, K. W., Hirsch, B. A., and MacDonald, C. C. (2006). 鈥淒ifferences in polyadenylation site choice between somatic and male germ cells.鈥� BMC Mol. Biol. 7, 35.
  • D鈥檓ello, V., Lee, J. Y., MacDonald, C. C., and Tian, B. (2006). 鈥淎lternative mRNA polyadenylation can potentially affect detection of gene expression by Affymetrix GeneChip庐 arrays.鈥� Applied Bioinformatics 5, 249鈥�253.
  • Huber, Z., Monarez, R. R., Dass, B., and MacDonald, C. C. (2005). 鈥淭he mRNA encoding 蟿CstF-64 is expressed ubiquitously in mouse and rat tissues.鈥� Ann. NY Acad. Sci. 1061, 163鈥�172.
  • Wallace, A. M., Denison, T. L., Attaya, E. N. and MacDonald, C. C. (2004). 鈥淒evelopmental differences in expression of two forms of the CstF-64 polyadenylation protein in rat and mouse.鈥� Biol. Reprod. 70, 1080鈥�1087.
  • Dass, B., McDaniel, L., Schultz, R. A., Attaya, E. and MacDonald, C. C. (2002). 鈥淭he gene CSTF2T encoding the human variant CstF-64 polyadenylation protein 蟿CstF-64 is intronless and may be associated with male sterility.鈥� Genomics 80, 509鈥�514.
  • Dass, B., Attaya, E. N., Wallace, A. M. and MacDonald, C. C. (2001). 鈥淥verexpression of the CstF-64 and CPSF-160 polyadenylation protein mRNAs in mouse male germ cells.鈥� Biol. Reprod. 64, 1722鈥�1729.
  • Dass, B., McMahon, K. W., Jenkins, N. A., Gilbert, D. J., Copeland, N. G. and MacDonald, C. C. (2001). 鈥淭he gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice.鈥� J. Biol. Chem. 276, 8044鈥�8050.