Genome-wide analysis reveals an unexpected function for the Drosophila splicing factor U2AF50 in the nuclear export of intronless mRNAs
Genome-wide analysis reveals an unexpected function for the Drosophila splicing factor U2AF50 in the nuclear export of intronless mRNAs
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DOI：
10.1016/j.molcel.2004.06.012
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发表时间：
2004-06-18
期刊：
影响因子：
16
通讯作者：
Rio, DC
中科院分区：
文献类型：
--
作者：
Blanchette, M;Labourier, E;Rio, DC
蛋白质因子U2AF是前mRNA剪接所需的重要组分。在S.利用粟酒裂殖酵母U2AF大亚基基因构建了温度敏感型U2AF大亚基转基因果蝇。突变体重组U2AF异二聚体显示在升高的温度下减少的聚嘧啶道RNA结合。全基因组RNA分析比较野生型和突变株确定了超过400个基因差异表达的dU2AF（50）突变苍蝇生长在限制性温度。令人惊讶的是，几乎40%的下调基因缺乏内含子。微阵列分析显示，在dU2AF的RNAi敲低的果蝇培养细胞中，大量无内含子mRNA的核输出受损（50）。核RNP复合物的免疫纯化显示，dU2AF（50）与无内含子的mRNA相关。这些结果揭示了剪接因子dU2AF（50）在无内含子mRNA的核输出中的意想不到的作用。
The protein factor U2AF is an essential component required for pre-mRNA splicing. Mutations identified in the S. pombe large U2AF subunit were used to engineer transgenic Drosophila carrying temperature-sensitive U2AF large subunit alleles. Mutant recombinant U2AF heterodimers showed reduced polypyrimidine tract RNA binding at elevated temperatures. Genome-wide RNA profiling comparing wild-type and mutant strains identified more than 400 genes differentially expressed in the dU2AF(50) mutant flies grown at the restrictive temperature. Surprisingly, almost 40% of the downregulated genes lack introns. Microarray analyses revealed that nuclear export of a large number of intronless mRNAs is impaired in Drosophila-cultured cells RNAi knocked down for dU2AF(50). Immunopurification of nuclear RNP complexes showed that dU2AF(50) associates with intronless mRNAs. These results reveal an unexpected role for the splicing factor dU2AF(50) in the nuclear export of intronless mRNAs.