RT Journal A1 Stoiber, Marcus H. A1 Olson, Sara A1 May, Gemma E. A1 Duff, Michael O. A1 Manent, Jan A1 Obar, Robert A1 Guruharsha, K.G. A1 Bickel, Peter J. A1 Artavanis-Tsakonas, Spyros A1 Brown, James B. A1 Graveley, Brenton R. A1 Celniker, Susan E. T1 Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila JF Genome Research JO Genome Research YR 2015 FD November 01 VO 25 IS 11 SP 1692 OP 1702 DO 10.1101/gr.182675.114 UL http://genome.cshlp.org/content/25/11/1692.abstract AB In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteins and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. From the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.