Authors: Lópe De Silanes, Isabel¹; Fan, Jinshui¹; Galbán, CRAIG J.²; Spencer, Richard G.²; Becker, Kevin G.³; Gorospe, Myriam¹

Source: Gene Expression, Volume 12, Number 1, 2004 , pp. 49-59(11)

Publisher: Cognizant Communication Corporation

Abstract:

HuR, a protein that binds to target mRNAs and can enhance their stability and translation, is increasingly recognized as a pivotal regulator of gene expression during cell division and tumorigenesis. We sought to identify collections of HuR-regulated mRNAs in colon cancer cells by systematic, cDNA array-based assessment of gene expression in three systems of varying complexity. First, comparison of gene expression profiles among tumors with different HuR abundance revealed highly divergent gene expression patterns, and virtually no changes in previously reported HuR target mRNAs. Assessment of gene expression patterns in a second system of reduced complexity, cultured colon cancer cells expressing different HuR levels, rendered more conserved sets of HuR-regulated mRNAs. However, the definitive identification of direct HuR target mRNAs required a third system of still lower complexity, wherein HuR–RNA complexes immunoprecipitated from colon cancer cells were subject to cDNA array hybridization to elucidate the endogenous HuR-bound mRNAs. Comparison of the transcript sets identified in each system revealed a strikingly limited overlap in HuR-regulated mRNAs. The data derived from this systematic analysis of HuR-regulated genes highlight the value of low-complexity, biochemical characterization of protein–RNA interactions. More importantly, however, the data underscore the broad usefulness of integrated approaches comprising systems of low complexity (protein–nucleic acid) and high complexity (cells, tumors) to comprehensively elucidate the gene regulatory events that underlie biological processes.

Keywords: cDNA arrays; RNA–protein complexes; Posttranscriptional regulation; mRNA turnover; Cancer model

Document Type: Review article

Affiliations: 1: Laboratory of Cellular and Molecular Biology 2: Laboratory of Clinical Investigation 3: Research Resources Branch, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224

Publication date: 2004-01-01

More about this publication?

• The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
  The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

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