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广泛的丝氨酸/精氨酸(SR)基因前体 mRNA 可变剪接与无义介导的衰变相偶联。

Extensive coupling of alternative splicing of pre-mRNAs of serine/arginine (SR) genes with nonsense-mediated decay.

机构信息

Department of Biology, Program in Molecular Plant Biology, Program in Cell and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.

出版信息

New Phytol. 2010 Jan;185(1):83-9. doi: 10.1111/j.1469-8137.2009.03065.x. Epub 2009 Oct 23.

DOI:10.1111/j.1469-8137.2009.03065.x
PMID:19863731
Abstract

In Arabidopsis, pre-mRNAs encoding serine/arginine (SR) proteins, key regulators of constitutive and alternative splicing, are extensively alternatively spliced. In seedlings, 13 SR genes are alternatively spliced to generate 75 transcripts, of which 53 contain a premature termination codon (PTC). However, it is not known if any of the PTC-containing splice variants are the targets of nonsense-mediated decay (NMD) and if there is any link between NMD and the abundance of functional transcripts. Here, we analyzed the abundances of all splice variants for each alternatively spliced gene in an Arabidopsis mutant that lacks UPF3, one of the core components of NMD machinery, to determine if the PTC-containing transcripts are degraded by NMD. Our results show that about half of the 53 splice variants with a PTC are the targets of degradation by NMD. The accumulation of PTC-containing transcripts resulted in concomitant reduction in the amount of functional transcript. These results show widespread coupling of alternative splicing with NMD in the SR gene family, suggesting a strong link between unproductive splicing and the abundance of functional transcripts.

摘要

在拟南芥中,编码丝氨酸/精氨酸(SR)蛋白的前体 mRNA 是组成性剪接和选择性剪接的关键调节因子,广泛存在选择性剪接。在幼苗中,13 个 SR 基因发生选择性剪接,生成 75 个转录本,其中 53 个包含过早终止密码子(PTC)。然而,尚不清楚是否有任何包含 PTC 的剪接变体是无义介导的降解(NMD)的靶标,以及 NMD 和功能转录本丰度之间是否存在任何联系。在这里,我们分析了缺乏 NMD 核心组件之一 UPF3 的拟南芥突变体中每个选择性剪接基因的所有剪接变体的丰度,以确定是否含有 PTC 的转录本被 NMD 降解。我们的结果表明,大约一半含有 PTC 的 53 个剪接变体是 NMD 降解的靶标。含有 PTC 的转录本的积累导致功能性转录本数量相应减少。这些结果表明,在 SR 基因家族中,选择性剪接与 NMD 广泛偶联,表明无效率剪接与功能转录本的丰度之间存在很强的联系。

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