Genome-wide Analysis of Alternative Pre-mRNA Splicing and RNA-Binding Specificities of the Drosophila hnRNP A/B Family Members
Genome-wide Analysis of Alternative Pre-mRNA Splicing and RNA-Binding Specificities of the Drosophila hnRNP A/B Family Members
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DOI：
10.1016/j.molcel.2009.01.022
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发表时间：
2009-02-27
期刊：
影响因子：
16
通讯作者：
Rio, Donald C.
中科院分区：
文献类型：
--
作者：
Blanchette, Marco;Green, Richard E.;Rio, Donald C.
传统上，异质的核核糖核蛋白（HNRNP）被视为蛋白质非特异性地包装RNA到核糖核蛋白颗粒中（RNP），但有证据表明，有证据表明对离散靶靶前MRNA的特定细胞功能提示。在这里，我们报告了由哺乳动物HNRNP A/B家族的四个果蝇同源物调节的替代剪接模式的全基因组分析（HRP36，HRP38，HRP40和HRP48）。对每种蛋白质的全局RNA结合分布的分析揭示了目标转录本上的小和广泛结合区域。 RNA的显着子集由多个HNRNP蛋白结合并调节，揭示了相互作用的组合网络。体外RNA结合位点选择实验（SELEX）鉴定了每种蛋白质的独特结合基序特异性，这些特异性在其各自的调节和结合转录本中的代表性过多。这些结果表明，单个异质核糖核蛋白具有特定的亲和力，可以重叠但独特的目标前MRNA的种群控制其RNA处理模式。
Heterogeneous nuclear ribonucleoproteins (hnRNPs) have been traditionally seen as proteins packaging RNA nonspecifically into ribonucleoprotein particles (RNPs), but evidence suggests specific cellular functions on discrete target pre-mRNAs. Here we report genome-wide analysis of alternative splicing patterns regulated by four Drosophila homologs of the mammalian hnRNP A/B family (hrp36, hrp38, hrp40, and hrp48). Analysis of the global RNA-binding distributions of each protein revealed both small and extensively bound regions on target transcripts. A significant subset of RNAs were bound and regulated by more than one hnRNP protein, revealing a combinatorial network of interactions. In vitro RNA-binding site selection experiments (SELEX) identified distinct binding motif specificities for each protein, which were overrepresented in their respective regulated and bound transcripts. These results indicate that individual heterogeneous ribonucleoproteins have specific affinities for overlapping, but distinct, populations of target pre-mRNAs controlling their patterns of RNA processing.