HRP-2, the Caenorhabditis elegans Homolog of Mammalian Heterogeneous Nuclear Ribonucleoproteins Q and R, Is an Alternative Splicing Factor That Binds to UCUAUC Splicing Regulatory Elements
HRP-2, the Caenorhabditis elegans Homolog of Mammalian Heterogeneous Nuclear Ribonucleoproteins Q and R, Is an Alternative Splicing Factor That Binds to UCUAUC Splicing Regulatory Elements
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DOI：
10.1074/jbc.m109.023101
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发表时间：
2009-10-16
影响因子：
4.8
通讯作者：
Zahler, Alan M.
中科院分区：
文献类型：
--
作者：
Kabat, Jennifer L.;Barberan-Soler, Sergio;Zahler, Alan M.
选择性剪接由前mRNA中的顺式序列调控，作为反式作用的选择性剪接因子的结合位点。在先前的研究中，我们利用生物信息学和分子生物学来鉴定和确认内含子六聚体序列UCUAUC是线虫的选择性剪接调控元件。在这项研究中，我们使用RNA亲和层析来鉴定与该序列结合的反式因子。HRP-2是人类异质性核糖核蛋白Q和R的秀丽线虫同源物，在UNC-52内含子调控序列的背景下与UCUAUC结合，也与包含该序列串联重复的RNA结合。六角体中的三个我们是这种结合特异性的最重要的决定因素。我们利用RNA干扰证明，HRP-2调控两个基因UNC-52和LIN-10的选择性剪接，这两个基因都有盒式外显子，两侧都有一个内含子UCUAUC基序。我们认为HRP-2是一种通过与UCUAUC序列结合而调节选择性剪接的蛋白质。
Alternative splicing is regulated by cis sequences in the pre-mRNA that serve as binding sites for trans-acting alternative splicing factors. In a previous study, we used bioinformatics and molecular biology to identify and confirm that the intronic hexamer sequence UCUAUC is a nematode alternative splicing regulatory element. In this study, we used RNA affinity chromatography to identify trans factors that bind to this sequence. HRP-2, the Caenorhabditis elegans homolog of human heterogeneous nuclear ribonucleoproteins Q and R, binds to UCUAUC in the context of unc-52 intronic regulatory sequences as well as to RNAs containing tandem repeats of this sequence. The three Us in the hexamer are the most important determinants of this binding specificity. We demonstrate, using RNA interference, that HRP-2 regulates the alternative splicing of two genes, unc-52 and lin-10, both of which have cassette exons flanked by an intronic UCUAUC motif. We propose that HRP-2 is a protein responsible for regulating alternative splicing through binding interactions with the UCUAUC sequence.