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mRNA 稳定性的变化在酵母细胞适应缺铁环境中起着重要作用。

Changes in mRNA stability play an important role in the adaptation of yeast cells to iron deprivation.

机构信息

Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), Agustín Escardino 7, E-46980 Paterna, Valencia, Spain.

Departamento de Genética, Universitat de València, Ave. Doctor Moliner 50, E-46100 Burjassot, Valencia, Spain; Instituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de València, Ave. Doctor Moliner 50, E-46100 Burjassot, Valencia, Spain.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2022 Feb;1865(2):194800. doi: 10.1016/j.bbagrm.2022.194800. Epub 2022 Feb 23.

Abstract

Eukaryotic cells rely on iron as an indispensable cofactor for multiple biological functions including mitochondrial respiration and protein synthesis. The budding yeast Saccharomyces cerevisiae utilizes both transcriptional and posttranscriptional mechanisms to couple mRNA levels to the requirements of iron deprivation. Thus, in response to iron deficiency, transcription factors Aft1 and Aft2 activate the expression of genes implicated in iron acquisition and mobilization, whereas two mRNA-binding proteins, Cth1 and Cth2, posttranscriptionally control iron metabolism. By using a genome-wide approach, we describe here a global stabilization of mRNAs, including transcripts encoding ribosomal proteins (RPs), when iron bioavailability diminishes. mRNA decay assays indicate that the mRNA-binding protein Pub1 contributes to RP transcript stabilization during adaptation to iron limitation. In fact, Pub1 becomes critical for growth and translational repression in low-iron conditions. Remarkably, we observe that pub1Δ cells also exhibit an increase in the transcription of RP genes that evidences the crosstalk between transcription and degradation mechanisms to maintain the appropriate mRNA balance under iron deficiency conditions.

摘要

真核细胞依赖铁作为多种生物功能(包括线粒体呼吸和蛋白质合成)不可缺少的辅助因子。酿酒酵母(Saccharomyces cerevisiae)利用转录和转录后机制将 mRNA 水平与缺铁的需求相偶联。因此,在缺铁时,转录因子 Aft1 和 Aft2 激活与铁摄取和动员相关的基因表达,而两个 mRNA 结合蛋白 Cth1 和 Cth2 在后转录水平上控制铁代谢。在这里,我们使用全基因组方法描述了在铁生物利用度降低时,mRNA 的全局稳定性,包括编码核糖体蛋白 (RP) 的转录本。mRNA 衰变测定表明,当适应缺铁时,mRNA 结合蛋白 Pub1 有助于 RP 转录本的稳定。事实上,Pub1 在低铁条件下对生长和翻译抑制变得至关重要。值得注意的是,我们观察到 pub1Δ 细胞中 RP 基因的转录也增加,这表明在缺铁条件下,转录和降解机制之间存在串扰,以维持适当的 mRNA 平衡。

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