Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila

Marcus H. Stoiber, Sara Olson, Gemma E. May, Michael O. Duff, Jan Manent, Robert Obar, K. G. Guruharsha, Peter J. Bickel, Spyros Artavanis-Tsakonas, James B. Brown, Brenton R. Graveley, Susan E. Celniker

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16 Citations (Scopus)


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 crossregulatory and hierarchical interactions in post-transcriptional control.

Original languageEnglish
Pages (from-to)1692-1702
Number of pages11
JournalGenome Research
Issue number11
Publication statusPublished - 1 Nov 2015
Externally publishedYes

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