Pbp1, the yeast ortholog of human Ataxin-2, functions in the cell growth on non-fermentable carbon sources.

Pbp1, the yeast ortholog of human Ataxin-2, functions in the cell growth on non-fermentable carbon sources.
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DOI:
10.1371/journal.pone.0251456
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Irie K
Irie K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tuong Vi DT;Fujii S;Valderrama AL;Ito A;Matsuura E;Nishihata A;Irie K;Suda Y;Mizuno T;Irie K

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Pbp1是人类Ataxin-2的酵母同源物,最初是作为聚(a)结合蛋白(Pab1)结合蛋白分离出来的。Pbp1调节Pan2-Pan3死烯化酶复合物,从而调节mRNA的稳定性和翻译效率。然而,Pbp1的生理意义尚不清楚,因为携带Pbp1缺失的酵母菌株在正常含葡萄糖培养基上的生长与野生型菌株相似。在这项研究中,我们发现Pbp1在含有不可发酵碳源的培养基上对细胞生长有作用。与野生型细胞相比,pbp1Δ突变体在含正常葡萄糖的培养基中表现出相似的生长,而pbp1Δ突变体在含甘油和乳酸的培养基中表现出较慢的生长。微阵列分析显示,参与糖异生的基因,如PCK1和FBP1,以及参与线粒体功能的基因,如COX10和COX11,在pbp1Δ突变体中表达减少。Pbp1通过启动子调控PCK1和FBP1的表达,而COX10和COX11的表达受Pbp1调控,而不是通过其启动子调控。在pbp1Δ突变体中,由于Dcp1脱帽酶或Xrn1 5 ‘ -3 ’外切酶的缺失,COX10和COX11的表达减少。我们的研究结果表明,Pbp1通过多种机制调节糖异生和线粒体功能相关基因的表达。
Pbp1, the yeast ortholog of human Ataxin-2, was originally isolated as a poly(A) binding protein (Pab1)-binding protein. Pbp1 regulates the Pan2-Pan3 deadenylase complex, thereby modulating the mRNA stability and translation efficiency. However, the physiological significance of Pbp1 remains unclear since a yeast strain harboring PBP1 deletion grows similarly to wild-type strain on normal glucose-containing medium. In this study, we found that Pbp1 has a role in cell growth on the medium containing non-fermentable carbon sources. While the pbp1Δ mutant showed a similar growth compared to the wild-type cell on a normal glucose-containing medium, the pbp1Δ mutant showed a slower growth on the medium containing glycerol and lactate. Microarray analyses revealed that expressions of the genes involved in gluconeogenesis, such as PCK1 and FBP1, and of the genes involved in mitochondrial function, such as COX10 and COX11, were decreased in the pbp1Δ mutant. Pbp1 regulated the expressions of PCK1 and FBP1 via their promoters, while the expressions of COX10 and COX11 were regulated by Pbp1, not through their promoters. The decreased expressions of COX10 and COX11 in the pbp1Δ mutant were recovered by the loss of Dcp1 decapping enzyme or Xrn1 5’-3’exonuclease. Our results suggest that Pbp1 regulates the expressions of the genes involved in gluconeogenesis and mitochondrial function through multiple mechanisms.
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