RNA Group, Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Mol Cell. 2011 Oct 7;44(1):108-19. doi: 10.1016/j.molcel.2011.06.035.
General discard pathways eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. In contrast to such general pre-mRNA 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.
一般的丢弃途径可以消除未加工和不规则的前体 mRNA，从而控制基因表达的质量。与这种一般的前体 mRNA 降解相反，我们在这里描述了一种核前体 mRNA 降解途径，它可以控制特定内含子基因的表达。我们表明，裂殖酵母核 poly(A)结合蛋白 Pab2 和核 exosome 亚基 Rrp6 是参与这种多聚腺苷酸化依赖的前体 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，低效剪接对于决定 Pab2 依赖的前体 mRNA 降解的易感性很重要。我们还表明，负剪接调节可以促进这种前体 mRNA 降解途径所需的不良剪接效率，并且通过这种方式，我们发现了通过核前体 mRNA 降解在核糖体蛋白的同源物之间进行交叉调节的机制。我们的发现揭示了细胞核中一种调节层，其中特定前体 mRNA 的周转，除了成熟 mRNA 的周转外，被用来控制基因表达。
