An apparent pseudo-exon acts both as an alternative exon that leads to nonsense-mediated decay and as a zero-length exon
An apparent pseudo-exon acts both as an alternative exon that leads to nonsense-mediated decay and as a zero-length exon
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DOI：
10.1128/mcb.26.6.2237-2246.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Smith, CWJ
中科院分区：
文献类型：
--
作者：
Grellscheid, SN;Smith, CWJ
假外显子是内含子序列，其侧翼是明显的共有剪接位点，但在剪接的mRNA中未观察到。假外显子通常很难通过突变激活，并且通常被视为对我们理解剪接体如何区分真实剪接位点和隐藏剪接位点的概念挑战。我们分析了一个明显的假外显子位于下游的互斥外显子和3的大鼠α-原肌球蛋白（TM）基因。TM假外显子在哺乳动物中是保守的，并且具有预测的剪接增强子和沉默子的保守谱，其比假外显子更典型地是真正的外显子。假外显子的剪接被完全激活，通过许多简单突变剪接到外显子3。预测假外显子与外显子3的剪接导致无义介导的衰变（NMD）。相比之下，当“预剪接”至外显子2时，其遵循“零长度外显子”剪接途径，其中在与外显子2的接合处新产生的5'剪接位点剪接至外显子4。我们建议，一个子集的明显的假外显子，如这里举例说明，实际上是真正的替代外显子，其包含导致NMD。
Pseudo-exons are intronic sequences that are flanked by apparent consensus splice sites but that are not observed in spliced mRNAs. Pseudo-exons are often difficult to activate by mutation and have typically been viewed as a conceptual challenge to our understanding of how the spliceosome discriminates between authentic and cryptic splice sites. We have analyzed an apparent pseudo-exon located downstream of mutually exclusive exons and 3 of the rat alpha-tropomyosin (TM) gene. The TM pseudo-exon is conserved among mammals and has a conserved profile of predicted splicing enhancers and silencers that is more typical of a genuine exon than a pseudo-exon. Splicing of the pseudo-exon is fully activated for splicing to exon 3 by a number of simple mutations. Splicing of the pseudo-exon to exon 3 is predicted to lead to nonsense-mediated decay (NMD). In contrast, when "prespliced" to exon 2 it follows a "zero length exon" splicing pathway in which a newly generated 5' splice site at the junction with exon 2 is spliced to exon 4. We propose that a subset of apparent pseudo-exons, as exemplified here, are actually authentic alternative exons whose inclusion leads to NMD.