Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila.
Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila.
复制标题
DOI：
10.1101/gr.182675.114
复制
发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Celniker SE
中科院分区：
文献类型：
--
作者：
Stoiber MH;Olson S;May GE;Duff MO;Manent J;Obar R;Guruharsha KG;Bickel PJ;Artavanis-Tsakonas S;Brown JB;Graveley BR;Celniker SE
在真核细胞中，RNA以核糖核蛋白颗粒（RNP）的形式存在。尽管这些复合物在许多生物过程中的重要性，包括剪接，多聚腺苷酸化，稳定性，运输，定位和翻译，其组成在很大程度上是未知的。我们亲和纯化20个不同的RNA结合蛋白（RBP）从培养的果蝇细胞在自然条件下，并确定了这些RNP复合物的RNA和蛋白质组合物。我们鉴定了与我们调查的大多数RBP相互作用的“高占有率靶”（HOT）RNA。HOT RNA编码无义介导的衰变和剪接机制的组分，以及RNA结合和翻译起始蛋白。RNP复合物含有参与RNA结合和转录后调节的蛋白质和mRNA。具有产生数百种mRNA亚型的能力的基因，超复杂基因，与异质核核糖核蛋白（hnRNP）广泛相互作用。我们的数据是一致的模型，其中RNP的子集包括来自同一基因的mRNA和蛋白质产物，表明广泛存在的自动调节RNP。从同时收购和RNP的蛋白质和RNA成分的综合分析，我们确定了广泛的交叉调节和层次的相互作用，在转录后控制。
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.