hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing
hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing
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DOI：
10.1093/emboj/18.14.4060
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发表时间：
1999-07-15
期刊：
影响因子：
11.4
通讯作者：
Zahler, AM
中科院分区：
文献类型：
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作者：
Caputi, M;Mayeda, A;Zahler, AM
人类免疫缺陷病毒1型（HIV-1）前体mRNA的剪接必须是低效的，以提供编码病毒蛋白并作为新病毒体基因组的未剪接信息库。负顺式调节元件（外显子剪接沉默子或ESS）是HIV-1剪接抑制所必需的。我们证明A和B组的异质核核糖核蛋白（hnRNP）是tnt外显子2 ESS功能所需的反式作用因子。从HeLa细胞核提取物中去除hnRNP A/B蛋白激活mt外显子2前体mRNA底物的剪接。通过将重组hnRNP A/B蛋白添加到耗尽的提取物中来恢复剪接抑制。hnRNP A 1结合序列可在功能上取代tnt外显子2的ESS。这些结果表明hnRNP A/B蛋白是抑制HIV-1剪接所必需的。
Splicing of the human immunodeficiency virus type 1 (HIV-1) pre-mRNA must be inefficient to provide a pool of unspliced messages which encode viral proteins and serve as genomes for new virions. Negative cis-regulatory elements (exonic splicing silencers or ESSs) are necessary for HIV-1 splicing inhibition. We demonstrate that heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A and B group are trans-acting factors required for the function of the tnt exon 2 ESS, Depletion of hnRNP A/B proteins from HeLa cell nuclear extract activates splicing of mt exon 2 pre-mRNA substrate. Splicing inhibition is restored by addition of recombinant hnRNP A/B proteins to the depleted extract. A high-affinity hnRNP A1-binding sequence can substitute functionally for the ESS in tnt exon 2, These results demonstrate that hnRNP A/B proteins are required for repression of HIV-1 splicing.