Oncoprotein TLS interacts with serine-arsnine proteins involved in RNA splicing
Oncoprotein TLS interacts with serine-arsnine proteins involved in RNA splicing
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DOI：
10.1074/jbc.273.43.27761
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发表时间：
1998-10-23
影响因子：
4.8
通讯作者：
Hickstein, DD
中科院分区：
文献类型：
--
作者：
Yang, L;Embree, LJ;Hickstein, DD
编码人TLS蛋白的基因，也称为FUS，位于人白血病和肉瘤中的染色体易位位点，在那里它与几种不同基因之一形成嵌合融合基因。为了鉴定TLS的相互作用伙伴，我们使用诱饵质粒中TLS的C-末端区域筛选从小鼠造血细胞构建的酵母双杂交cDNA文库。分离了编码丝氨酸-精氨酸（SR）蛋白家族成员的两个cDNA。第一个SR蛋白是人剪接因子SC 35的小鼠同源物，第二个SR成员是一种新的183个氨基酸的蛋白，我们称之为TASR（TLS相关丝氨酸精氨酸蛋白）。人TASR的cDNA克隆表明小鼠和人TASR具有相同的氨基酸序列。TLS和这两个SR蛋白之间的相互作用通过共转染和免疫沉淀研究证实。体内剪接实验表明，SC 35和TASR影响腺病毒E1 A前体mRNA的剪接位点选择。TLS可以通过与其C-末端区域的相互作用将SR剪接因子募集到特定的靶基因，并且截短TLS的C-末端区域的染色体易位可以阻止这种相互作用。因此，TLS易位可能改变RNA加工并在恶性转化中发挥作用。
The gene encoding the human TLS protein, also termed FUS, is located at the site of chromosomal translocations in human leukemias and sarcomas where it forms a chimeric fusion gene with one of several different genes. To identify interacting partners of TLS, we screened a yeast two-hybrid cDNA library constructed from mouse hematopoietic cells using the C-terminal region of TLS in the bait plasmid. Two cDNAs encoding members of the serine-arginine (SR) family of proteins were isolated. The first SR protein is the mouse homolog of human splicing factor SC35, and the second SR member is a novel 183-amino acid protein that we term TASR (TLS-associated serine-arginine protein). cDNA cloning of human TASR indicated that mouse and human TASR have identical amino acid sequences. The interactions between TLS and these two SR proteins were confirmed by co-transfection and immunoprecipitation studies. In vivo splicing assays indicated that SC35 and TASR influence splice site selection of adenovirus E1A pre-mRNA. TLS may recruit SR splicing factors to specific target genes through interaction with its C-terminal region, and chromosomal translocations that truncate the C-terminal region of TLS may prevent this interaction. Thus TLS translocations may alter RNA processing and play a role in malignant transformation.