Identification of alternative splicing regulators by RNA interference in Drosphila
Identification of alternative splicing regulators by RNA interference in Drosphila
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DOI：
10.1073/pnas.0407004101
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发表时间：
2004-11-09
影响因子：
11.1
通讯作者：
Graveley, BR
中科院分区：
文献类型：
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作者：
Park, JW;Parisky, K;Graveley, BR
选择性剪接被认为是由非剪接体RNA结合蛋白调节的，非剪接体RNA结合蛋白调节剪接体核心组分与前mrna的关联。虽然大多数后生动物基因编码的pre- mrna可选择性剪接，但目前已知的剪接调节因子非常少。在这里，我们使用RNA干扰来检测bbbb70 %的果蝇RNA结合蛋白在调节选择性剪接中的作用。我们确定了47种蛋白作为剪接调节因子，其中26种以前没有涉及选择性剪接。我们发现的许多调节因子是非剪接体rna结合蛋白。然而，我们的筛选出乎意料地显示，改变剪接体某些核心成分的浓度特异性地调节了选择性剪接。这些结果显著扩大了已知剪接调节因子的数量，并揭示了调节选择性剪接的机制的非凡丰富性。
Alternative splicing is thought to be regulated by nonspliceosomal RNA binding proteins that modulate the association of core components of the spliceosome with the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are alternatively spliced, remarkably few splicing regulators are currently known. Here, we used RNA interference to examine the role of >70% of the Drosophila RNA-binding proteins in regulating alternative splicing. We identified 47 proteins as splicing regulators, 26 of which have not previously been implicated in alternative splicing. Many of the regulators we identified are nonspliceosomal RNA-binding proteins. However, our screen unexpectedly revealed that altering the concentration of certain core components of the spliceosome specifically modulates alternative splicing. These results significantly expand the number of known splicing regulators and reveal an extraordinary richness in the mechanisms that regulate alternative splicing.