Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome

Following transcription and splicing, each mRNA of a mammalian cell passes into the cytoplasm where its fate is in the hands of a complex network of r ibonucleoproteins (mRNPs). The success or failure of a gene to be expressed depends on the performance of this mRNP infrastructure. The entry, gating, processing, and transit of each mRNA through an mRNP network helps determi ne the composition of a cell's proteome. The machinery that regulates stora ge, turnover, and translational activation of mRNAs is not well understood, in part, because of the heterogeneous nature of mRNPs. Recently, subsets o f cellular mRNAs clustered as members of mRNP complexes have been identifie d by using antibodies reactive with RNA-binding proteins, including ELAV/Hu , eIF-4E, and poly(A)-binding proteins. Cytoplasmic ELAV/Hu proteins are in volved in the stability and translation of early response gene (ERG) transc ripts and are expressed predominately in neurons. mRNAs recovered from ELAV /Hu mRNP complexes were found to have similar sequence elements, suggesting a common structural linkage among them. This approach opens the possibilit y of identifying transcripts physically clustered in vivo that may have sim ilar fates or functions. Moreover, the proteins encoded by physically organ ized mRNAs may participate in the same biological process or structural out come, not unlike operons and their polycistronic mRNAs do in prokaryotic or ganisms. Our goal is to understand the organization and flow of genetic inf ormation on an integrative systems level by analyzing the collective proper ties of proteins and mRNAs associated with mRNPs in vivo.