title: Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila.
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.
authors: Department of Biostatistics, University of California Berkeley, Berkeley, California 94720, USA; Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Marcus H
authors: MH
authors: Stoiber
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Sara
authors: S
authors: Olson
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Gemma E
authors: GE
authors: May
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Michael O
authors: MO
authors: Duff
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
authors: Jan
authors: J
authors: Manent
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
authors: Robert
authors: R
authors: Obar
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; Biogen Incorporated, Cambridge, Massachusetts 02142, USA;
authors: K G
authors: KG
authors: Guruharsha
authors: Department of Biostatistics, University of California Berkeley, Berkeley, California 94720, USA;
authors: Peter J
authors: PJ
authors: Bickel
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; Biogen Incorporated, Cambridge, Massachusetts 02142, USA;
authors: Spyros
authors: S
authors: Artavanis-Tsakonas
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA; Department of Statistics, University of California Berkeley, Berkeley, California 94720, USA.
authors: James B
authors: JB
authors: Brown
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Brenton R
authors: BR
authors: Graveley
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Susan E
authors: SE
authors: Celniker
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins