RNA binding proteins (RBPs) are emerging as multifunctional entities that act on the mRNA biogenesis pathway from transcription initiation through translation and decay. Association of RBPs with mRNAs through untranslated sequence elements has been proposed to constitute a mechanism that allows for the coordination of gene expression at the post-transcriptional level, defining post-transcriptional operons (Keene, 2002). We have recently characterized the mRNA interactome of two human mRNA binding proteins (Gama-Carvalho, 2006). Classification of the target mRNAs into Gene Ontology (GO) groups suggests that each protein associates with functionally coherent mRNA populations, supporting a coordinating role in gene expression. To understand whether these RNA populations contain distinctive sequence elements we have performed sequence motif searchs for consensus binding sites in the whole transcript, coding sequence and UTRs and compared to a non-associated mRNA population. The results support the model of differential interaction between functionally related mRNA populations and specific regulatory RNA binding proteins through the presence of untranslated sequence elements for regulation (USER) codes. Identification of potential gene networks in the population of target mRNAs using the Ingenuity Pathways KnowledgeBase suggests that these proteins may be involved in the coordination of key cellular functions and signaling pathways, with potential antagonistic effects. We have obtained preliminary evidence for regulatory functions of both proteins on their target mRNAs and we now aim to model these RNA-protein interaction networks and their effects on gene expression, as well as to develop methods to identify USER codes involved in the post-transcriptional coordination of gene expression.