User:Jeff Coller

Education
University of Michigan 1990-1994 (BS in Biology/Chemistry)

Stockholm University 1993 (Visiting Scientist)

University of Wisconsin-Madison 1994-2000 (Ph.D. in Cell and Molecular Biology)

Howard Hughes Medical Institute / University of Arizona 2000-2005 (Post-doctoral Fellow)

Bio
I have a long standing fascination with the study of RNA that dates back more than 15 years. My interest stems from undergraduate work I conducted on group I introns in Dr. Britt-Marie Sjöberg’s lab at Stockholm University in Sweden. Following that experience, I was drawn to the University of Wisconsin-Madison for graduate school where I immersed myself in the rich culture of RNA research that occurs at that institution. My Ph.D. work was performed in the lab of Dr. Marv Wickens; I was attracted to Marv’s lab because I was fascinated by the observation that most early developmental decisions in the embryo do not occur as a consequence of gene transcription, rather, most are made by regulating the translational status of maternal mRNAs. Following completion of my graduate work, I continued to study the process of mRNA translation as a Post-doc in Dr. Roy Parker’s lab (University of Arizona, HHMI). During the course of our work, Roy and I realized that the active regulation of mRNA translation is not an event reserved solely for the embryo, rather, it most likely occurs in all cells and is ancient in origin. I recently left Roy’s lab as I was most fortunate to have the opportunity to start my own lab in an environment renowned for its RNA community, Case Western Reserve University (CWRU). Now, as a primary investigator in the Center for RNA Molecular Biology at CWRU, I continue to explore an intriguing aspect of gene expression that involves the active movement of mRNA in and out of translation.

Primary Appointment
Assistant Professor in the Center for RNA Molecular Biology

Secondary Appointment
Department of Biochemistry

Biomedical Sciences Training Program

Research Interest
Gene expression is tightly regulated at each step to ensure accurate communication of instruction from DNA to proteins. To safeguard the fidelity of gene expression, downstream events must be tightly controlled as not to mask the regulatory events that have occurred upstream. For example, repression of mRNA transcription at the DNA level in response to a cue would be irrelevant to overall gene expression if the cytoplasmic pool of transcribed mRNAs were able to be constantly translated. One important and poorly understood step of gene expression, therefore, is cessation of mRNA translation. We have determined that the exiting of mRNAs from translation and into quiescence occurs in an active and regulated fashion thereby protecting the linear movement of genetic information from transcription to translation.

Our studies indicate that cessation of mRNA translation does not occur in a passive, or default manner, but rather, when the functional lifetime of an mRNA has ended, ribosomes are actively dissociated from the mRNA. Specifically, we have demonstrated that the DEAD-box RNA helicase, Dhh1p, is required for the dissociation of mRNA from the translational apparatus. This activity and mechanism of gene regulation is conserved throughout eukaryotes. For example, the Dhh1p homologue is required for repressing maternal mRNA expression in frog and fly oocytes. In addition, the homologue of Dhh1p in worms, clam and mouse is associated with complexes that contain translationally inactive mRNAs, and regulation of expression of these mRNAs by Dhh1p is critical for proper embryogenesis. Lastly, the human homologue of Dhh1p, RCK/p54, has been found to associate with granules in the cell cytoplasm that contain the miRNA/siRNA machinery, and has recently been shown to be required for translational repression by miRNA.

We believe that the active removal of mRNA from translation by Dhh1p-like helicases is an ancient and conserved step in mRNA expression designed to provide fine-tune control of gene regulation. This mechanism of regulating gene expression is utilized to control the translation of mRNAs that have outlived their functional lifetime, and certain mRNAs have evolved to specifically interact with the basal Dhh1p machinery thereby facilitating translational control of specific mRNAs under various cellular conditions. We have, therefore, uncovered a previously unanticipated but clearly vital aspect of gene regulation. Our goal is to detail the mechanism by which mRNA cease translating and the cellular cues that lead to this event

Publications
Sweet, T.J, Boyer, B., Hu, W., Baker, K.E., and Coller, J. (2007) Microtubule disruption stimulates P-body formation. RNA, in press.

Barbee, S., Estes, P., Cziko, AM., Luedeman, R., Coller, J., Johnson, N., Howlett, I., MacDonald, P., Brand, A., Newbury, S., Levine, R., Wilhelm, J., Nakamura, A., Parker, R., and Ramaswami, R. (2006) Neuronal RNA granules and cytoplasmic processing bodies are similar in composition and function. Neuron, 21:997-1009

Coller J., and Parker R. (2005) General Translational Repression by Activators of mRNA Decapping. Cell 122:875-886.

Cheng Z., Coller J., Parker R., and Song H. (2005) Crystal structure of the DEAD box helicase, Dhh1p. RNA 11:1258-1270.

Baker K.E.*, Coller J.*, and Parker R. (2004) The yeast Apq12 protein affects nucleocytoplasmic mRNA transport. RNA 10:1352-1358.


 * Authors contributed equally

Coller J., Tucker M., Sheth U., Valencia M., and Parker R. (2001) The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 12:1717-1727.

Coller J. (2000) Control of mRNA metabolism via the poly (A) binding protein and development of the tethered function assay. Doctorate Thesis, University of Wisconsin.

Gray N., Coller J., Dickson K., and Wickens M. (2000) Multiple portions of poly (A) binding protein stimulate translation in vivo through a poly (A)-independent mechanism. EMBO J 19:4723-4733.

Coller J., Gray N., and Wickens M. (1998) mRNA stabilization by poly (A) binding protein is independent of a poly (A) tail and requires translation. Genes & Dev. 12:3226-3235.

Reviews and Chapters
Coller J. and Wickens, M. (2007). The tethered function assay: an adaptable approach to studying mRNA binding proteins. Methods in Enzyl. in prep.

Baker, K.E. and Coller J., (2006) Post-transcriptional control of gene expression: regulating mRNA translation. Genome Biology 7:332.

Coller J., and Parker R. (2004) Eukaryotic mRNA decapping. Annu. Rev. Biochem. 73:861-890.

Coller J., and Wickens M. (2002) Tethered function assays using 3’UTRs. Methods 26:142-150.

Contact Information
Jeff Coller, Ph.D., Assistant Professor

Center for RNA Molecular Biology Case Western Reserve University School of Medicine Wood Bldg. W113 10900 Euclid Ave. Cleveland OH 44106-4960 USA

jmc71@case.edu

T 216-368-0299 C 216-543-3258 F 216-368-2010

www.case.edu/med/coller

Coller, Jeff Coller, Jeff