Park Jung W, Parisky Katherine, Celotto Alicia M, Reenan Robert A, Graveley Brenton R
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301, USA.
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15974-9. doi: 10.1073/pnas.0407004101. Epub 2004 Oct 18.
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.
可变剪接被认为受非剪接体RNA结合蛋白调控,这些蛋白可调节剪接体核心组分与前体mRNA的结合。尽管大多数后生动物基因编码的前体mRNA会发生可变剪接,但目前已知的剪接调节因子却非常少。在此,我们利用RNA干扰技术研究了果蝇中70%以上的RNA结合蛋白在调控可变剪接中的作用。我们鉴定出47种蛋白作为剪接调节因子,其中26种此前未被认为与可变剪接有关。我们鉴定出的许多调节因子都是非剪接体RNA结合蛋白。然而,我们的筛选意外地发现,改变剪接体某些核心组分的浓度会特异性地调节可变剪接。这些结果显著增加了已知剪接调节因子的数量,并揭示了调控可变剪接机制的异常丰富性。