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带有哺乳动物密码子偏好的 mRNA 在组成型应激颗粒的酵母突变体中积累。

mRNA with Mammalian Codon Bias Accumulates in Yeast Mutants with Constitutive Stress Granules.

机构信息

Centre de Biophysique Moléculaire, UPR 4301 du CNRS, Rue Charles Sadron, 45071 Orléans, France.

Colléguim Sciences et Techniques, Université d'Orléans, 45071 Orléans, France.

出版信息

Int J Mol Sci. 2020 Feb 12;21(4):1234. doi: 10.3390/ijms21041234.

DOI:10.3390/ijms21041234
PMID:32059599
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072924/
Abstract

Stress granules and P bodies are cytoplasmic structures assembled in response to various stress factors and represent sites of temporary storage or decay of mRNAs. Depending on the source of stress, the formation of these structures may be driven by distinct mechanisms, but several stresses have been shown to stabilize mRNAs via inhibition of deadenylation. A recent study identified yeast gene deletion mutants with constitutive stress granules and elevated P bodies; however, the mechanisms which trigger its formation remain poorly understood. Here, we investigate the possibility of accumulating mRNA with mammalian codon bias, which we termed the model RNA, in these mutants. We found that the model RNA accumulates in and mutants and in four mutants with constitutive stress granules overlapping with P bodies. However, in eight other mutants with constitutive stress granules, the model RNA is downregulated, or its steady state levels vary. We further suggest that the accumulation of the model RNA is linked to its protection from the main mRNA surveillance path. However, there is no obvious targeting of the model RNA to stress granules or P bodies. Thus, accumulation of the model RNA and formation of constitutive stress granules occur independently and only some paths inducing formation of constitutive stress granules will stabilize mRNA as well.

摘要

应激颗粒和 P 体是在响应各种应激因素时组装的细胞质结构,代表 mRNA 暂时储存或降解的场所。根据应激源的不同,这些结构的形成可能由不同的机制驱动,但已有研究表明,几种应激会通过抑制腺苷酸化来稳定 mRNA。最近的一项研究鉴定出酵母基因缺失突变体,它们具有组成型应激颗粒和升高的 P 体;然而,其形成的机制仍知之甚少。在这里,我们研究了在这些突变体中积累具有哺乳动物密码子偏性的 mRNA 的可能性,我们将其称为模型 RNA。我们发现模型 RNA 在 和 突变体以及与 P 体重叠的四个具有组成型应激颗粒的突变体中积累。然而,在另外八个具有组成型应激颗粒的突变体中,模型 RNA 的表达被下调,或者其稳态水平发生变化。我们进一步提出,模型 RNA 的积累与其免受主要 mRNA 监测途径的保护有关。然而,模型 RNA 并没有明显地靶向应激颗粒或 P 体。因此,模型 RNA 的积累和组成型应激颗粒的形成是独立发生的,只有一些诱导组成型应激颗粒形成的途径也会稳定 mRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/d6f257a0b826/ijms-21-01234-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/bd4e3e096ec0/ijms-21-01234-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/a90638f5a1a3/ijms-21-01234-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/d6f257a0b826/ijms-21-01234-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/bd4e3e096ec0/ijms-21-01234-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f20/7072924/e79c4254dfd0/ijms-21-01234-g002.jpg
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