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J. Biol. Chem., Vol. 279, Issue 31, 32839-32847, July 30, 2004

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DLP, a Novel Dim1 Family Protein Implicated in Pre-mRNA Splicing and Cell Cycle Progression^*

Xiaojing Sun¶, Hua Zhang, Dan Wang, Dalong Ma¶, Yan Shen¶||, and Yongfeng Shang**

From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, the National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100005, and the ^¶Chinese National Human Genome Center, Beijing 100176, China

In eukaryotes, primary transcripts undergo a splicing process that removes intronic sequences by a macromolecular enzyme known as the spliceosome. Both genetic and biochemical studies have revealed that essential components of the spliceosome include five small RNAs, U1, U2, U4, U5, and U6, and as many as 300 distinct proteins. Here we report the molecular cloning and functional analysis of a novel cDNA encoding for a protein of 149 amino acids. This protein has 38% amino acid sequence identity with and is evolutionally related to yeast Dim1 protein. Hence we named this protein DLP for Dim1-like protein. We showed that DLP is required for S/G₂ transition. We also demonstrated that DLP functions in cell nucleus and interacts with the U5-102-kDa protein subunit of the spliceosome, and blocking DLP protein activity led to an insufficient pre-mRNA splicing, suggesting that DLP is yet another protein component involved in pre-mRNA splicing. Collectively, our experiments indicated that DLP is implicated in not only cell cycle progression but also in a more specific molecular process such as pre-mRNA splicing.

Received for publication, March 5, 2004 , and in revised form, May 6, 2004.

^* This work was supported by grants from the Chinese National Key Program on Basic Research (Grant G1998051003 to Y. She.), the Chinese National High-Tech R&D Program (Grant 863-102-10-03-05 to Y. She. and 2002BA711A01-05 to Y. Sha.), and the National Natural Science Foundation of China (Grants 39625007 and 39993420 to Y. She. and 30225043 and 30393110 to Y. Sha.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence may be addressed. Tel.: 86-10-8280-5118; Fax: 86-10-8280-1355; E-mail: jason{at}bjmu.edu.cn.

^|| To whom correspondence may be addressed. Tel.: 86-10-6529-6486; Fax: 86-10-6526-3392; E-mail: sheny{at}ms.imicams.ac.cn.

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