학술논문

Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila
Document Type
article
Source
Genome Research. 25(11)
Subject
Biochemistry and Cell Biology
Bioinformatics and Computational Biology
Genetics
Biological Sciences
Human Genome
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
Drosophila Proteins
Drosophila melanogaster
Gene Expression Regulation
Heterogeneous-Nuclear Ribonucleoproteins
RNA Splicing
RNA
Messenger
RNA-Binding Proteins
Sequence Analysis
RNA
Transfection
Medical and Health Sciences
Bioinformatics
Language
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.