A Pre-mRNA Degradation Pathway that Selectively Targets Intron-Containing Genes Requires the Nuclear Poly(A)-Binding Protein
A Pre-mRNA Degradation Pathway that Selectively Targets Intron-Containing Genes Requires the Nuclear Poly(A)-Binding Protein
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DOI：
10.1016/j.molcel.2011.06.035
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发表时间：
2011-10-07
期刊：
影响因子：
16
通讯作者：
Bachand, Francois
中科院分区：
文献类型：
--
作者：
Lemieux, Caroline;Marguerat, Samuel;Bachand, Francois
一般的丢弃途径消除了未经处理和不规则的前mRNAs，以控制基因表达的质量。与这种一般的Prem-RNA衰变不同，我们在这里描述了一种控制特定内含子基因表达的核前mRNA降解途径。我们证明，裂解酵母核多聚(A)结合蛋白Pab2和核外切体亚单位RRP6是参与这一依赖于多聚腺苷的Pre-mRNA降解途径的主要因素。转录组分析和内含子交换实验表明，低效剪接是决定Pab2依赖的Pre-mRNA衰退的易感性的重要因素。我们还表明，负剪接调控可以促进这一前mRNA衰退途径所需的低剪接效率，在这样做的过程中，我们确定了一种通过核前mRNA衰退在平行核糖体蛋白之间进行交叉调控的机制。我们的发现揭示了细胞核中的一层调控，在这一层中，特定前mRNAs的周转，除了成熟mRNAs的周转外，还被用来控制基因表达。
General discard pathways eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. In contrast to such general prem-RNA decay, we describe here a nuclear pre-mRNA degradation pathway that controls the expression of select intron-containing genes. We show that the fission yeast nuclear poly(A)-binding protein, Pab2, and the nuclear exosome subunit, Rrp6, are the main factors involved in this polyadenylation-dependent pre-mRNA degradation pathway. Transcriptome analysis and intron swapping experiments revealed that inefficient splicing is important to dictate susceptibility to Pab2-dependent pre-mRNA decay. We also show that negative splicing regulation can promote the poor splicing efficiency required for this pre-mRNA decay pathway, and in doing so, we identified a mechanism of cross-regulation between paralogous ribosomal proteins through nuclear pre-mRNA decay. Our findings unveil a layer of regulation in the nucleus in which the turnover of specific pre-mRNAs, besides the turnover of mature mRNAs, is used to control gene expression.