Pasteur Institute-Cenci Bolognetti Foundation, Department of Biology and Biotechnology Charles Darwin, University of Rome Sapienza, Piazzale Aldo Moro 5, Rome, Italy.
Cell Cycle. 2010 Oct 1;9(19):3991-6. doi: 10.4161/cc.9.19.13210. Epub 2010 Oct 29.
Expression of the histone genes is tightly coupled to rates of DNA synthesis in yeast and histone mRNAs are modulated both transcriptionally and post-transcriptionally. Trf4 and Trf5, poly(A) polymerases, that mediates polyadenylation and consequent degradation) and Rrp6, an exosome component, play a role in the regulation of histone mRNA levels. In this paper we show that in the mRNA degradation mutant Kllsm4Δ1, histone mRNAs are induced early in the S-phase and maintained at high level all along the entire cell cycle due to a delay in the exit from S-phase and/or entry into M-phase. The overexpression of the HIR1 gene (Histone transcriptional repressor), previously isolated as a multicopy suppressor of the apoptotic phenotypes observed in Kllsm4Δ1, can also restore the normal cycling of histone genes expression. We also found that low doses of hydroxyurea neutralize the onset of the apoptotic phenotypes in Kllsm4Δ1, as well in another mRNA decapping mutants (lsm1) and, in addition, increase the chronological lifespan in both strains suggesting that an entry delay into the S phase can recover some cellular defects in decapping mutants.
组蛋白基因的表达与酵母中的 DNA 合成速率密切相关，组蛋白 mRNA 的转录和转录后均受到调节。Trf4 和 Trf5（介导多聚腺苷酸化和随后降解的多聚（A）聚合酶）和 Rrp6（外切体成分）在组蛋白 mRNA 水平的调节中发挥作用。在本文中，我们表明在 mRNA 降解突变体 Kllsm4Δ1 中，由于 S 期退出和/或进入 M 期的延迟，组蛋白 mRNA 在 S 期早期被诱导，并在整个细胞周期中维持在高水平。先前作为 Kllsm4Δ1 中观察到的凋亡表型的多拷贝抑制因子分离的 HIR1 基因（组蛋白转录抑制剂）的过表达也可以恢复组蛋白基因表达的正常循环。我们还发现低剂量的羟基脲可以中和 Kllsm4Δ1 中凋亡表型的出现，以及另一种 mRNA 去帽突变体（lsm1），此外，在两种菌株中都增加了时序寿命，这表明进入 S 期的延迟可以恢复去帽突变体中的一些细胞缺陷。
