Ross Buchan

Associate Professor, Molecular and Cellular Biology

We study stress granules and P-bodies; a dynamic duo of gel-like bodies that affect the function of mRNAs, the templates of protein synthesis. 

 

In the Buchan lab, we use yeast and cell line models to study the architecture of the cytoplasmic mRNP cycle.  Our overall goal is to better understand what factors and processes affect the function of specific mRNAs, and how defects in this cycle may contribute to various disease states.

The control of gene expression is critical to nearly all aspects of cellular biology, from maintaining basic cell function and identity, to the ability of cells to respond to numerous signals that arise during processes such as development, exposure to pathogens or changes in the cellular environment.  A key means by which all eukaryotic cells enact appropriate gene expression responses is to alter the function of messenger RNAs (mRNAs).  mRNAs exist in different functional states, dependent upon the proteins bound to them.  These states include translation (protein synthesis), repression (off state) and decay.  The localization of an mRNAs can also affect its function, thus cells are offered an array of spatial and temporal mechanisms for gene expression control at the mRNA level.

mRNAs can also cycle between these different functional states.  For example, mRNAs exiting translation often accumulate in distinct mRNA-protein (mRNP) assemblies known as P-bodies and stress granules, from which they may ultimately return to translation again.  P-bodies and stress granules are conserved throughout eukaryotes, contain important protein regulators of decay and translation, and thus affect gene expression control.  In addition, they strongly resemble other important mRNP granules that function in embryogenesis (maternal granules) and memory formation (neuronal transport granules).  Finally, these granules have numerous connections to disease, such as an involvement in RNA viral replication, elevated levels in certain cancer types, as well as the formation of apparently aberrant stress granules in neurodegenerative diseases.

 

Publications

2021

Bearss, J. J., S. Kr Padi, N. Singh, M. Cardo-Vila, J. H. Song, G. Mouneimne, N. Fernandes, Y. Li, M. R. Harter, J. Mc Gard, et al., "EDC3 phosphorylation regulates growth and invasion through controlling P-body formation and dynamics.", EMBO Rep, pp. e50835, 2021 Feb 15. PMID: 33586867

2020

Liu, G., A. Byrd, A. N. Warner, F. Pei, E. Basha, A. Buchanan, and R. J Buchan, "Cdc48/VCP and Endocytosis Regulate TDP-43 and FUS Toxicity and Turnover.", Mol Cell Biol, vol. 40, issue 4, 2020 01 30. PMCID: PMC6996276 PMID: 31767634
Eshleman, N., X. Luo, A. Capaldi, and R. J Buchan, "Alterations of signaling pathways in response to chemical perturbations used to measure mRNA decay rates in yeast.", RNA, vol. 26, issue 1, pp. 10-18, 2020 01. PMCID: PMC6913126 PMID: 31601735
Fernandes, N., L. Nero, S. M. Lyons, P. Ivanov, T. M. Mittelmeier, T. A. Bolger, and R. J Buchan, "Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation.", Biomolecules, vol. 10, issue 10, 2020 Sep 25. PMCID: PMC7650667 PMID: 32992901
Fernandes, N., and R. J Buchan, "RPS28B mRNA acts as a scaffold promoting cis-translational interaction of proteins driving P-body assembly.", Nucleic Acids Res, vol. 48, issue 11, pp. 6265-6279, 2020 06 19. PMCID: PMC7293044 PMID: 32396167

2018

Fernandes, N., N. Eshleman, and R. J Buchan, "Stress Granules and ALS: A Case of Causation or Correlation?", Adv Neurobiol, vol. 20, pp. 173-212, 2018. PMID: 29916020

2017

Liu, G., A. N. Coyne, F. Pei, S. Vaughan, M. Chaung, D. C. Zarnescu, and R. J Buchan, "Endocytosis regulates TDP-43 toxicity and turnover.", Nat Commun, vol. 8, issue 1, pp. 2092, 2017 12 12. PMCID: PMC5727062 PMID: 29233983
Liu, G., C. Lanham, R. J Buchan, and M. E. Kaplan, "High-throughput transformation of Saccharomyces cerevisiae using liquid handling robots.", PLoS One, vol. 12, issue 3, pp. e0174128, 2017. PMCID: PMC5358765 PMID: 28319150
Liu, G., F. Pei, F. Yang, L. Li, A. Dipak Amin, S. Liu, R. J Buchan, and W. C. Cho, "Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer.", Int J Mol Sci, vol. 18, issue 2, 2017 Feb 10. PMCID: PMC5343902 PMID: 28208579

2016

Eshleman, N., G. Liu, K. McGrath, R. Parker, and R. J Buchan, "Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy.", RNA, vol. 22, issue 8, pp. 1200-14, 2016 08. PMCID: PMC4931113 PMID: 27251550

2014

J Buchan, R., "mRNP granules. Assembly, function, and connections with disease.", RNA Biol, vol. 11, issue 8, pp. 1019-30, 2014. PMCID: PMC4615263 PMID: 25531407

2013

J Buchan, R., R-M. Kolaitis, P. J Taylor, and R. Parker, "Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function.", Cell, vol. 153, issue 7, pp. 1461-74, 2013 Jun 20. PMCID: PMC3760148 PMID: 23791177

2012

J Buchan, R., A. P. Capaldi, and R. Parker, "TOR-tured yeast find a new way to stand the heat.", Mol Cell, vol. 47, issue 2, pp. 155-7, 2012 Jul 27. PMID: 22841000

2011

J Buchan, R., J-H. Yoon, and R. Parker, "Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae.", J Cell Sci, vol. 124, issue Pt 2, pp. 228-39, 2011 Jan 15. PMCID: PMC3010191 PMID: 21172806

2010

J Buchan, R., T. Nissan, and R. Parker, "Analyzing P-bodies and stress granules in Saccharomyces cerevisiae.", Methods Enzymol, vol. 470, pp. 619-40, 2010. PMID: 20946828

2009

J Buchan, R., and R. Parker, "Eukaryotic stress granules: the ins and outs of translation.", Mol Cell, vol. 36, issue 6, pp. 932-41, 2009 Dec 25. PMCID: PMC2813218 PMID: 20064460

2008

J Buchan, R., D. Muhlrad, and R. Parker, "P bodies promote stress granule assembly in Saccharomyces cerevisiae.", J Cell Biol, vol. 183, issue 3, pp. 441-55, 2008 Nov 03. PMCID: PMC2575786 PMID: 18981231

2007

J Buchan, R., and R. Parker, "Molecular biology. The two faces of miRNA.", Science, vol. 318, issue 5858, pp. 1877-8, 2007 Dec 21. PMID: 18096794
J Buchan, R., and I. Stansfield, "Halting a cellular production line: responses to ribosomal pausing during translation.", Biol Cell, vol. 99, issue 9, pp. 475-87, 2007 Sep. PMID: 17696878

2006

J Buchan, R., L. S. Aucott, and I. Stansfield, "tRNA properties help shape codon pair preferences in open reading frames.", Nucleic Acids Res, vol. 34, issue 3, pp. 1015-27, 2006. PMCID: PMC1363775 PMID: 16473853