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Jeff Coller, Ph.D.

Associate Professor, Center for RNA Molecular Biology (Faculty since 2005)

JeffColler02

Education: Ph.D.: Biochemistry, University of Wisconsin-Madison, 1999

Postdoc: Howard Hughes Medical Insitute, University of Arizona, 2005

Secondary Appointment in: Department of Biochemistry

Email: jmc71

Office Location: Wood Blgd. W113

Office Phone: 216-368-0299

Office FAX: 216-368-2010

Laboratory Location: W119

Laboratory Phone: 216-368-0276

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Curriculum Vitae

Lab Link

Research:  Regulation of mRNA

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 and onset of mRNA degradation.

A majority of mRNA decay initiates by shortening the 3’ polyadenosine tail (deadenylation), followed by 5’ cap cleavage (decapping), and 5’-3’ exonucleolytic digestion. Deadenylation occurs when mRNA is actively translated, however, decapping and exonucleolytic decay are postulated to occur after ribosomes are cleared and in the cytoplasmic structures termed P-bodies. Several correlations support this hypothesis. First, decapping rate is reciprocally proportional to translational initiation rate. Moreover, decapping regulators directly repress translation, and these and additional decay factors and mRNA decay intermediates co-localize in ribosome-free P-bodies. Finally, P-body size and abundance are inversely proportional with mRNA translation and decay status in the cell. Despite these observations, recent findings suggest mRNA degradation may be independent of P-bodies. Specifically, P-body disruption or formation, under certain conditions, is uncoupled from alternations in mRNA translation or mRNA decay. Consequently, an important but unresolved issue is to determine the interplay between translation and mRNA decay and determine the context in which mRNA is degraded.

We have recently shown that decapping and 5’-3’ degradation of mRNA can occur when the transcripts are associated with actively translating ribosomes (Hu et al., 2009). Specifically, our recent work has demonstrated that mRNA remains associated with active ribosomes during the process of mRNA decapping and exonucleolytic degradation. The data clearly indicate that sequestration into a ribosome-free state (e.g. P-bodies) is not a prerequisite for initiation of mRNA decay. These findings are consistent with the demonstration in yeast, Drosophila, and humans that mRNA metabolism can be uncoupled from P-body formation. Our findings raise several interesting mechanistic questions, for instance how mRNA half-lives are determined in the context of on-going translation. Moreover, it is unclear how the decapping machinery associates and functions on an actively translating mRNA.

Finally, co-translational mRNA degradation makes sense from an evolutionary point of view. Specifically, the three steps of decay each serve to systematically limit translational events without interfering with them. Deadenylation may reduce translational efficiency perhaps through loss of the poly(A) binding protein, Pab1p or association of decapping regulators. mRNA decapping inhibits further translation initiation events. Finally, degradation from the 5’ end while the mRNA is ribosome associated ensures decay does not impede residual ribosomes undergoing translocation. In this way, the final polypeptide expressed prior to the mRNA being destroyed is full length and functional.

Publications

 

Pubmed Link to Publications

Google Scholar Link to Publications

 

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Smith, J.E., Alvarez-Dominguez, J.R., Kline, N., Huynh, N., Geisler, S., Hu, W., Coller, J., and Baker, K.E. (2014). Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae. Cell Reports, in press

Sweet, T.J., Kovalak, C., and Coller, J., (2012) The DEAD-box Protein Dhh1 Promotes Decapping by Slowing Ribosome Movement. PLoS Biology., 10(6):1-15.

Hu, W., and Coller, J., (2012) What comes first: translational repression or mRNA degradation? The deepening mystery of microRNA function. Cell Research, doi:10.1038/cr.2012.80.

Geisler, S., Lojek, L., Khalil, A., Baker, K.E., and Coller, J., (2012) A decapping pathway for long non-coding RNAs regulates inducible genes. Mol Cell, 45(3): 279-291. (Previewed by Wilkinson and colleagues)

Castellani, R. J., Gupta, Y., Sheng, B., Siedlak, S. L., Harris, P. L., Coller, J. M., Perry, G., Lee, H.-G., Tabaton, M., Smith, M. A., et al. (2011). A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease: parallels to stress granules. Lab. Invest. 91, 1777–1786.

Blewett, N., Coller, J., and Goldstrohm A. (2011). A quantitative assay for measuring mRNA decapping by splinted ligation reverse transcription polymerase chain reaction: qSL-RT-PCR. RNA, 17:535-543

Geisler, S. and Coller, J. (2010). Alternate endings - A new story for mRNA decapping. Mol Cell, 40: 349-350

Hu, W., Petzold, C., Coller, J., and Baker, K.E. (2010). Nonsense-mediated mRNA decapping occurs on polyribosomes in Saccharomyces cerevisiae. Nat. Struct. Mol. Biol., 17: 244-247

Hu, W., Sweet, T., Chamnongpol, S., Baker, K., and Coller, J. (2009) Co-translational mRNA decay in Saccharomyces cerevisiae. Nature, 461: 225-229.

Sweet, T.J, Boyer, B., Hu, W., Baker, K.E., and Coller, J. (2007) Microtubule disruption stimulates P-body formation. RNA, 13: 493-502.

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

Geisler, S. and Coller, J. (2013) RNA in unexpected places: long noncoding RNAs function in a variety of cellular contexts. Nature Reviews Molecular Cell Biology, doi:10.1038/nrm3679

Hu, W. and Coller, J.(2013) Polyribosome analysis for determining mRNA and ribosome association in Saccharomyces cerevisiae. Methods Enzymol. 530:193-206.

Hu, W. and Coller, J.(2013) Method for measuring mRNA decay rates in Saccharomyces cerevisiae. Methods Enzymol. 530:137-55.

Khalil, A. and Coller, J. editors. (2013) The Molecular Biology of Non-coding RNA. Springer Science

Presnyak, V., and Coller, J. (2013). The DHH1/RCKp54 family of helicases: An ancient family of proteins that promote translational silencing. Biochimica et Biophysica Acta. 1829:817-823.

Geisler, S. and Coller, J. (2012) XRN1: A major 5' to 3' exoribonuclease in eukaryotic cells. The Enzymes, 31:1-20.

Coller, J. and Rueda, D. (2009) RNA research in the Rustbelt. RNA Biol. 6:9-11

Coller J. (2008). Methods to determine mRNA half-life in Saccharomyces cerevisiae Methods Enzymol. 448:267-84.

Coller J. and Wickens, M. (2007). Tethered function assays: An adaptable approach to study RNA regulatory proteins Methods Enzymol. 429:299-321

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.

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