Beyond the Identification of Transcribed Sequences:
Functional, Evolutionary and Expression Analysis
12th International Workshop
October 25-28, 2002
Washington, DC

List of Abstracts * Speakers * Organizers * Authors * Original Announcement

Array Analysis of mRNP Complexes Reveals Clustered mRNA Subsets that May Represent Posttranscriptional Operons

Scott A. Tenenbaum and Jack D. Keene
Department of Molecular Genetics and Microbiology and The Center for RNA Biology, Duke University Medical Center, Durham, NC 27710 USA
Telephone: 919 684-2714
Fax: 919 684-8735

RNA-binding proteins are essential in regulating posttranscriptional gene-expression in eukaryotes and are responsible for generating much of the diversity of the proteome.  We have developed methods for purifying endogenously formed mRNP-complexes that, when coupled with microarray technologies, allow the rapid identification of multiple mRNA targets, quantitatively, and en masse (Tenenbaum et al. (2002) Methods 26, 191). The primary steps involved in characterizing mRNA subsets clustered by mRNA-associated proteins include; (1) isolation of endogenously formed mRNP complexes, (2) en masse identification of clustered mRNA subsets using array analysis, (3) identification of similar cis-elements among clustered mRNAs, and (4) determination of functional relationships among the protein products coded for by the mRNAs in a subset.  This ribonomics approach has been used to identify unique mRNA profiles for several RNA-binding proteins including ELAV/HuB (Tenenbaum et al. (2000) PNAS 97, 14085), FMRP (Brown et al. (2001) Cell 107, 477), and a recently identified autoantigen GW182 (Eystathioy et al., (2002) MBC, 13, 1338). 

The ribonomics approach to functional genomics has revealed three novel findings; (1) mRNA binding proteins are associated with unique subpopulations of messages, 2) the composition of these mRNA subsets can vary with cellular conditions and (3) the same mRNA species can be found in multiple mRNP complexes. Based on these data, we proposed a model of posttranscriptional gene expression in which mRNA-binding proteins regulate mRNAs as fluctuating subpopulations (Keene and Tenenbaum (2002) Molecular Cell 9, 1161. This model predicts that functionally related genes are regulated posttranscriptionally as subpopulations by specificmRNA-binding proteins that recognize sequence elements in common among the clustered mRNA transcripts. This suggests that an mRNP infrastructure exists within mammalian cells consisting of mRNAs that are networked by multi-targeted RNA-binding proteins.  If subpopulations of monocistronic mRNAs are coordinately regulated en masse, their protein products may participate in the same biological process or pathway, thereby providing a posttranscriptional analog to the polycistronic operon.  The combinatorial reassortment of mRNA transcripts associated with RNA-binding proteins (termed quasigenomes) can bring together the ingredients needed for a variety of complex functions and phenotypes while utilizing a relatively small number of genes.

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