Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila
- Marcus H. Stoiber1,
- Sara Olson2,
- Gemma E. May2,
- Michael O. Duff2,
- Jan Manent3,
- Robert Obar3,
- Kuthethur Guruharsha3,
- Spyros Artavanis-Tsakonas3,
- James B. Brown4,
- Brenton R. Graveley2 and
- Susan E Celniker4,5
- 1 University of California, Berkeley;
- 2 University of Connecticut Health Center;
- 3 Harvard Medical School;
- 4 Lawrence Berkeley National Laboratory
- ↵* Corresponding author; email: celniker{at}fruitfly.org
Abstract
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, ultra-complex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data is 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.
- Received August 7, 2014.
- Accepted June 10, 2015.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.
