保守内含子元件在体外抑制神经元特异性c-src外显子的剪接。
Conserved intron elements repress splicing of a neuron-specific c-src exon in vitro.
作者信息
Chan R C, Black D L
机构信息
Molecular Biology Institute, University of California at Los Angeles 90095, USA.
出版信息
Mol Cell Biol. 1995 Nov;15(11):6377-85. doi: 10.1128/MCB.15.11.6377.
Abstract
The neuron-specific N1 exon of the mouse c-src transcript is normally skipped in nonneuronal cells. In this study, we examined the sequence requirements for the exclusion of this exon in nonneuronal HeLa cell nuclear extracts. We found that the repression of the N1 exon is mediated by specific intron sequences that flank the N1 exon. Mutagenesis experiments identified conserved CUCUCU elements within these intron regions that are required for the repression of N1 splicing. The addition of an RNA competitor containing the upstream regulatory sequence to the HeLa extract induced splicing of the intron downstream of N1, indicating that the competitor sequence binds to splicing repressor proteins. The similarities between this mechanism for src splicing repression and the repression of other regulated exons point to a common role of exon-spanning interactions in splicing repression.
摘要
小鼠c-src转录本中神经元特异性的N1外显子在非神经元细胞中通常被跳过。在本研究中，我们检测了非神经元HeLa细胞核提取物中排除该外显子的序列要求。我们发现N1外显子的抑制是由位于N1外显子两侧的特定内含子序列介导的。诱变实验确定了这些内含子区域内保守的CUCUCU元件，它们是抑制N1剪接所必需的。向HeLa提取物中添加含有上游调控序列的RNA竞争物可诱导N1下游内含子的剪接，这表明竞争物序列与剪接抑制蛋白结合。src剪接抑制机制与其他受调控外显子的抑制之间的相似性表明，外显子跨度相互作用在剪接抑制中具有共同作用。
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