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Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2017-11-20 , DOI: 10.1093/nar/gkx1160
Debasish Sarkar , Sunirmal Paira , Biswadip Das

Unfolded protein response (UPR) is triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which is accomplished by a dramatic induction of genes encoding ER chaperones. Activation of these genes involves their rapid transcription by Hac1p, encoded by the HAC1 precursor transcript harboring an intron and a bipartite element (3′-BE) in the 3′-UTR. ER stress facilitates intracellular targeting and recruitment of HAC1 pre-mRNA to Ire1p foci (requiring 3′-BE), leading to its non-spliceosomal splicing mediated by Ire1p/Rlg1p. A critical concentration of the pre-HAC1 harboring a functional 3′-BE element is governed by its 3′→5′ decay by the nuclear exosome/DRN. In the absence of stress, pre-HAC1 mRNA undergoes a rapid and kinetic 3′→5′ decay leading to a precursor pool, the majority of which lack the BE element. Stress, in contrast, causes a diminished decay, thus resulting in the production of a population with an increased abundance of pre-HAC1 mRNA carrying an intact BE, which facilitates its more efficient recruitment to Ire1p foci. This mechanism plays a crucial role in the timely activation of UPR and its prompt attenuation following the accomplishment of homeostasis. Thus, a kinetic mRNA decay provides a novel paradigm for mRNA targeting and regulation of gene expression.

中文翻译:

核mRNA降解调节酿酒酵母中未折叠的蛋白质反应的获得

未折叠的蛋白应答(UPR)由内质网(ER)中未折叠的蛋白的积累触发,这是通过编码ER伴侣蛋白的基因的大量诱导而实现的。这些基因的激活涉及它们通过Hac1p的快速转录,由Hac1p前体转录本编码,该转录本在3'-UTR中包含一个内含子和一个二聚体元件(3'-BE)。内质网应激促进细胞内靶向和HAC1前mRNA募集到Ire1p病灶(需要3'-BE),导致其由Ire1p / Rlg1p介导的非剪接体剪接。带有功能性3'-BE元素的pre- HAC1的临界浓度受核外泌体/ DRN的3'→5'衰减控制。在没有压力的情况下,HAC1之前mRNA经历了快速的动力学3'→5'衰减,导致前体池,其中大多数缺少BE元素。相反,压力导致衰减减少,因此导致携带完整BE的HAC1之前mRNA丰度增加的种群产生,这有助于其更有效地募集到Ire1p病灶。该机制在UPR的及时激活及其在体内稳态完成后的迅速衰减中起着至关重要的作用。因此,动态的mRNA衰减为mRNA靶向和基因表达调控提供了新的范例。
更新日期:2017-11-20
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