Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins
Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins
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DOI：
10.1016/s0014-4827(02)00046-0
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发表时间：
2003-02-15
影响因子：
3.7
通讯作者：
Barta, A
中科院分区：
文献类型：
--
作者：
Meissner, M;Lopato, S;Barta, A
TLS/FUS是一种核酸结合蛋白，其N-末端的一半在人白血病和脂肪肉瘤中发现的融合癌蛋白中作为转录激活域发挥作用。以前的报道表明TLS/FUS在转录和剪接过程中的作用。在这里，我们报告TLS/FUS与核基质的关联，并研究其在剪接中的作用。在TLS/FUS免疫缺失提取物中，两种前mRNA的拼接受到抑制，并且只能通过添加重组TLS/FUS或/和SR蛋白（TLS/FUS的已知相互作用伙伴）来部分恢复。随后对TLS/FUS免疫沉淀物的分析显示，除了SR蛋白SC 35和SRp 75之外，剪接因子PTB（hnRNPI）和剪接辅激活因子SRm 160与TLS/FUS复合，从而解释了不能完全恢复剪接的原因。共免疫定位证实了TLS/FUS与PTB、SR蛋白和SRm 160的核基质缔合和相互作用。我们的研究结果表明，基质蛋白TLS/FUS在剪接体组装中发挥作用。(C)2003 Elsevier Science（美国）。All rights reserved.
TLS/FUS is a nucleic acid-binding protein whose N-terminal half functions as a transcriptional activator domain in fusion oncoproteins found in human leukemias and liposarcomas. Previous reports have suggested a role for TLS/FUS in transcription and splicing processes. Here we report the association of TLS/FUS with the nuclear matrix and investigate its role in splicing. Splicing of two pre-mRNAs was inhibited in a TLS/FUS-immunodepleted extract and could only be partly restored by addition of recombinant TLS/FUS or/and SR proteins, known interaction partners of TLS/FUS. The subsequent analysis of TLS/FUS immunoprecipitates revealed that, in addition to the SR proteins SC35 and SRp75, the splicing factor PTB (hnRNPI) and the splicing coactivator SRm160 are complexed with TLS/FUS, thus explaining the inability to restore splicing completely. Coimmunolocalization confirmed the nuclear matrix association and interaction of TLS/FUS with PTB, SR proteins, and SRm 160. Our results suggest that the matrix protein TLS/FUS plays a role in spliceosome assembly. (C) 2003 Elsevier Science (USA). All rights reserved.