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Nucleic Acids Research Advance Access published online on September 25, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp787
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

tRNA over-expression in breast cancer and functional consequences

Mariana Pavon-Eternod1, Suzanna Gomes2, Renaud Geslain1, Qing Dai1, Marsha Rich Rosner2,* and Tao Pan1,*

1Department of Biochemistry and Molecular Biology and 2Ben May Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA

*To whom correspondence should be addressed. Tel: 773-702-0380; Fax: 773-702-4476; Email: m-rosner{at}uchicago.edu Correspondence may also be addressed to Tao Pan. Tel: 773-702-4179; Fax: 773-702-0439; Email: taopan{at}uchicago.edu

Received April 20, 2009. Revised September 3, 2009. Accepted September 6, 2009.

Increased proliferation and elevated levels of protein synthesis are characteristics of transformed and tumor cells. Though components of the translation machinery are often misregulated in cancers, what role tRNA plays in cancer cells has not been explored. We compare genome-wide tRNA expression in cancer-derived versus non-cancer-derived breast cell lines, as well as tRNA expression in breast tumors versus normal breast tissues. In cancer-derived versus non-cancer-derived cell lines, nuclear-encoded tRNAs increase by up to 3-fold and mitochondrial-encoded tRNAs increase by up to 5-fold. In tumors versus normal breast tissues, both nuclear- and mitochondrial-encoded tRNAs increase up to 10-fold. This tRNA over-expression is selective and coordinates with the properties of cognate amino acids. Nuclear- and mitochondrial-encoded tRNAs exhibit distinct expression patterns, indicating that tRNAs can be used as biomarkers for breast cancer. We also performed association analysis for codon usage-tRNA expression for the cell lines. tRNA isoacceptor expression levels are not geared towards optimal translation of house-keeping or cell line specific genes. Instead, tRNA isoacceptor expression levels may favor the translation of cancer-related genes having regulatory roles. Our results suggest a functional consequence of tRNA over-expression in tumor cells. tRNA isoacceptor over-expression may increase the translational efficiency of genes relevant to cancer development and progression.


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