SUS1 introns are required for efficient mRNA nuclear export in yeast.

SUS1 introns are required for efficient mRNA nuclear export in yeast.
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DOI:
10.1093/nar/gkr496
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发表时间:
2011-10
影响因子:
14.9
通讯作者:
Rodríguez-Navarro S
Rodríguez-Navarro S
中科院分区:
生物学2区
文献类型:
--
作者:
Cuenca-Bono B;García-Molinero V;Pascual-García P;Dopazo H;Llopis A;Vilardell J;Rodríguez-Navarro S

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mRNA合成和输出之间的有效偶联对于基因表达至关重要。Sus 1/ENY 2是佐贺和TREX-2复合物的一个组分,参与转录和mRNA输出。虽然大多数酵母基因缺乏内含子,我们以前报道,酵母SUS 1轴承两个。在这里,我们表明,这个功能是进化保守的和关键的Sus 1功能。我们确定,虽然SUS 1剪接是低效的,它响应细胞条件,内含子突变促进或阻断剪接导致mRNA输出和细胞生长的缺陷。与此相一致,我们发现,内含子较少的SUS 1只能部分挽救suS 1 Δ表型。值得注意的是,每个SUS 1内含子的剪接也受到另一个内含子和SUS 1外显子序列的影响。此外,通过跟踪SUS 1 RNA和蛋白水平,我们确定了无义介导的衰变(NMD)途径和剪接因子Mud 2都在SUS 1表达中起作用。我们的数据(以及Hossain等人的相关工作)提供证据表明剪接,翻译和衰变参与mRNP生物发生的早期事件的调节,并暗示额外的要求,从一个单一的基因剪接异构体的平衡。
Efficient coupling between mRNA synthesis and export is essential for gene expression. Sus1/ENY2, a component of the SAGA and TREX-2 complexes, is involved in both transcription and mRNA export. While most yeast genes lack introns, we previously reported that yeast SUS1 bears two. Here we show that this feature is evolutionarily conserved and critical for Sus1 function. We determine that while SUS1 splicing is inefficient, it responds to cellular conditions, and intronic mutations either promoting or blocking splicing lead to defects in mRNA export and cell growth. Consistent with this, we find that an intron-less SUS1 only partially rescues sus1Δ phenotypes. Remarkably, splicing of each SUS1 intron is also affected by the presence of the other and by SUS1 exonic sequences. Moreover, by following SUS1 RNA and protein levels we establish that nonsense-mediated decay (NMD) pathway and the splicing factor Mud2 both play a role in SUS1 expression. Our data (and those of the accompanying work by Hossain et al.) provide evidence of the involvement of splicing, translation, and decay in the regulation of early events in mRNP biogenesis; and imply the additional requirement for a balance in splicing isoforms from a single gene.
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