Insights into the selective activation of alternatively used splice acceptors by the human immunodeficiency virus type-1 bidirectional splicing enhancer.

Insights into the selective activation of alternatively used splice acceptors by the human immunodeficiency virus type-1 bidirectional splicing enhancer.
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对人类免疫缺陷病毒类型1型双向剪接增强剂的选择性激活的选择性激活。

DOI:
10.1093/nar/gkm1147
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发表时间:
2008-03
影响因子:
14.9
通讯作者:
Schaal, Heiner
Schaal, Heiner
中科院分区:
生物学2区
文献类型:
--
作者:
Asang, Corinna;Hauber, Ilona;Schaal, Heiner

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在人类免疫缺陷病毒1型(HIV-1)前体mRNA的外显子5中发现的富含鸟苷腺苷的外显子剪接增强子(GAR ESE)在SR蛋白SF 2/ASF 2和SRp 40存在下激活1-内含子报告基因构建体中的增强子依赖性5′剪接位点(ss)或3′ ss。对HIV-1外显子5内部GAR ESE的作用模式进行表征后,我们发现该增强子具有双重剪接调控功能:(i)通过其单个SR蛋白结合位点协同介导外显子识别;(ii)在外显子5前的3′ ss簇内赋予3′ ss选择性。这两种功能都依赖于GAR ESE、U1 snRNP在下游5′ ss D4处的结合以及位于这些元件之间的E42序列。因此,跨外显子相互作用的网络似乎调节选择性外显子4a和5的剪接。由于GAR增强子介导的上游3′ ss簇的激活对于在中间病毒基因表达期间加工含内含子的vpu/env-mRNA也是必不可少的,因此GAR增强子实质上有助于调节病毒复制。
The guanosine-adenosine-rich exonic splicing enhancer (GAR ESE) identified in exon 5 of the human immunodeficiency virus type-1 (HIV-1) pre-mRNA activates either an enhancer-dependent 5′ splice site (ss) or 3′ ss in 1-intron reporter constructs in the presence of the SR proteins SF2/ASF2 and SRp40. Characterizing the mode of action of the GAR ESE inside the internal HIV-1 exon 5 we found that this enhancer fulfils a dual splicing regulatory function (i) by synergistically mediating exon recognition through its individual SR protein-binding sites and (ii) by conferring 3′ ss selectivity within the 3′ ss cluster preceding exon 5. Both functions depend upon the GAR ESE, U1 snRNP binding at the downstream 5′ ss D4 and the E42 sequence located between these elements. Therefore, a network of cross-exon interactions appears to regulate splicing of the alternative exons 4a and 5. As the GAR ESE-mediated activation of the upstream 3′ ss cluster also is essential for the processing of intron-containing vpu/env-mRNAs during intermediate viral gene expression, the GAR enhancer substantially contributes to the regulation of viral replication.
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发表时间: 2003-07-01
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