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Genome Res. 2015 Nov;25(11):1692-702. doi: 10.1101/gr.182675.114. Epub 2015 Aug 20.

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

Author information

1
Department of Biostatistics, University of California Berkeley, Berkeley, California 94720, USA; Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
2
Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
3
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
4
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; Biogen Incorporated, Cambridge, Massachusetts 02142, USA;
5
Department of Biostatistics, University of California Berkeley, Berkeley, California 94720, USA;
6
Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA; Department of Statistics, University of California Berkeley, Berkeley, California 94720, USA.
7
Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;

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, 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.

PMID:
26294687
PMCID:
PMC4617965
DOI:
10.1101/gr.182675.114
[Indexed for MEDLINE]
Free PMC Article

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