Cyclin L is an RS domain protein involved in pre-mRNA splicing
Cyclin L is an RS domain protein involved in pre-mRNA splicing
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DOI：
10.1074/jbc.m202266200
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发表时间：
2002-07-12
影响因子：
4.8
通讯作者：
Gottesfeld, JM
中科院分区：
文献类型：
--
作者：
Dickinson, LA;Edgar, AJ;Gottesfeld, JM
我们报道了人类细胞周期蛋白L的cDNA克隆和功能表征，这是一种与参与RNA聚合酶II （pol II）转录调控的c型细胞周期蛋白相关的新型细胞周期蛋白。Cyclin L还含有一个交替的精氨酸和丝氨酸的cooh末端二肽重复序列，这是SR剪接因子家族的一个标志。我们发现重组cyclin L与p110 PITSLRE激酶相互作用，并且cyclin L抗体共同免疫沉淀HeLa核提取物的激酶活性，使pol II的羧基末端结构域（CTD）和剪接因子SC35磷酸化，并被cdk抑制剂p21抑制。Cyclin L抗体在体外抑制RNA剪接的第二步，重组Cyclin L蛋白在次优条件下刺激剪接。值得注意的是，p21抑制剪接的lC（50）与抑制细胞周期蛋白l相关激酶活性的lC（50）相似。因此，细胞周期蛋白L及其相关激酶是前mrna加工机制的新成员。
We report the cDNA cloning and functional characterization of human cyclin L, a novel cyclin related to the C-type cyclins that are involved in regulation of RNA polymerase II (pol II) transcription. Cyclin L also contains a COOH-terminal dipeptide repeat of alternating arginines and serines, a hallmark of the SR family of splicing factors. We show that recombinant cyclin L interacts with p110 PITSLRE kinase, and that cyclin L antibody co-immunoprecipitates a kinase activity from HeLa nuclear extracts that phosphorylates the carboxyl-terminal domain (CTD) of pol II and splicing factor SC35, and is inhibited by the cdk inhibitor p21. Cyclin L antibody inhibits the second step of RNA splicing in vitro, and recombinant cyclin L protein stimulates splicing under suboptimal conditions. Significantly, the lC(50) for splicing inhibition by p21 is similar to the lC(50) for inhibition of the cyclin L-associated kinase activity. Cyclin L and its associated kinase are thus new members of the pre-mRNA processing machinery.