Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Genes Cells. 2021 Jun;26(6):381-398. doi: 10.1111/gtc.12846. Epub 2021 Apr 13.
CCR4 and POP2 genes encode the catalytic subunit of the Ccr4-Not complex involved in shortening mRNA poly(A) tail in Saccharomyces cerevisiae. The ccr4Δ and pop2∆ mutants exhibit pleiotropic phenotypes such as slow and temperature-sensitive growth, aberrant expression of glucose repression genes and abnormal cell wall synthesis. We previously found that the growth defect of the ccr4Δ and pop2∆ mutants is suppressed by deletion of the PBP1 gene, which encodes poly(A)-binding protein (Pab1)-binding protein 1. In this study, we investigated the functional relationship between Ccr4/Pop2 and Pbp1 by measuring changes in gene expression in ccr4Δ and pop2∆ single mutants and ccr4Δ pbp1∆ and pop2∆ pbp1∆ double mutants. We found that expression of HSP12, HSP26, PIR3, FUS1 and GPH1 was increased in ccr4Δ and pop2∆ single mutants. The pbp1∆ mutation not only restored the growth defect but also reduced the increased expression of those genes found in the ccr4Δ and pop2∆ mutants. Over-expression of PBP1 in the ccr4Δ mutant further increased the expression of HSP12, HSP26, PIR3 and FUS1 and exacerbated the cell growth. These results suggest that the aberrant expression of a subset of genes, which is facilitated by Pbp1, contributes to the pleiotropic phenotypes of the ccr4Δ and pop2∆ mutants.
CCR4 和 POP2 基因编码参与酿酒酵母 mRNA 多聚(A)尾缩短的 Ccr4-Not 复合物的催化亚基。 ccr4Δ 和 pop2∆ 突变体表现出多种表型,如生长缓慢和温度敏感、葡萄糖抑制基因表达异常和细胞壁合成异常。我们之前发现,缺失编码多聚(A)结合蛋白(Pab1)结合蛋白 1 的 PBP1 基因可抑制 ccr4Δ 和 pop2∆ 突变体的生长缺陷。在这项研究中,我们通过测量 ccr4Δ 和 pop2∆ 单突变体和 ccr4Δ pbp1∆ 和 pop2∆ pbp1∆ 双突变体中基因表达的变化,研究了 Ccr4/Pop2 和 Pbp1 之间的功能关系。我们发现,在 ccr4Δ 和 pop2∆ 单突变体中,HSP12、HSP26、PIR3、FUS1 和 GPH1 的表达增加。 pbp1∆ 突变不仅恢复了生长缺陷,而且降低了 ccr4Δ 和 pop2∆ 突变体中发现的这些基因的表达增加。在 ccr4Δ 突变体中过表达 PBP1 进一步增加了 HSP12、HSP26、PIR3 和 FUS1 的表达,并加剧了细胞生长。这些结果表明,由 Pbp1 促进的一组特定基因的异常表达有助于 ccr4Δ 和 pop2∆ 突变体的多种表型。