Rph1 coordinates transcription of ribosomal protein genes and ribosomal RNAs to control cell growth under nutrient stress conditions
Rph1 coordinates transcription of ribosomal protein genes and ribosomal RNAs to control cell growth under nutrient stress conditions
复制标题
Rph1 协调核糖体蛋白基因和核糖体 RNA 的转录，以控制营养胁迫条件下的细胞生长
DOI：
10.1093/nar/gkaa558
复制
发表时间：
2020-07
影响因子：
14.9
通讯作者：
Du Hai-Ning
中科院分区：
文献类型：
--
作者：
Shu Wen-Jie;Chen Runfa;Yin Zhao-Hong;Li Feng;Zhang Heng;Du Hai-Ning
摘要真核RNA聚合酶(RNAP)对核糖体RNA(RRNA)合成和核糖体蛋白基因(RPG)转录的协调调控是生长控制的关键。尽管RNPI依赖的35S rRNA的产生和RNAPII介导的RPG转录之间存在平衡的证据已经被描述，但其分子基础仍然不清楚。在这里，我们发现Rph1调节酵母中rRNAs和RPG的转录状态。我们发现Rph1与RNAPI和RNAPII转录的基因广泛相关。RPH1基因的缺失通过抑制rRNA和RPG转录，显著缓解了营养胁迫条件下TORC1抑制引起的细胞生长缓慢。从机制上讲，Rim15激酶在雷帕霉素治疗后使Rph1磷酸化。与野生型相比，Rph1的磷酸化模拟突变体对雷帕霉素的处理表现出更强的抗性，与核糖体相关基因的关联减少，细胞生长更快，这表明Rph1从染色质中解离出来确保了细胞在营养胁迫下的存活。我们的结果揭示了Rph1在协调RNA聚合酶介导的转录以控制营养胁迫条件下细胞生长的作用。
Abstract Coordinated regulation of ribosomal RNA (rRNA) synthesis and ribosomal protein gene (RPG) transcription by eukaryotic RNA polymerases (RNAP) is a key requirement for growth control. Although evidence for balance between RNPI-dependent 35S rRNA production and RNAPII-mediated RPG transcription have been described, the molecular basis is still obscure. Here, we found that Rph1 modulates the transcription status of both rRNAs and RPGs in yeast. We show that Rph1 widely associates with RNAPI and RNAPII-transcribed genes. Deletion of RPH1 remarkably alleviates cell slow growth caused by TORC1 inhibition via derepression of rRNA and RPG transcription under nutrient stress conditions. Mechanistically, Rim15 kinase phosphorylates Rph1 upon rapamycin treatment. Phosphorylation-mimetic mutant of Rph1 exhibited more resistance to rapamycin treatment, decreased association with ribosome-related genes, and faster cell growth compared to the wild-type, indicating that Rph1 dissociation from chromatin ensures cell survival upon nutrient stress. Our results uncover the role of Rph1 in coordination of RNA polymerases-mediated transcription to control cell growth under nutrient stress conditions.
登录
查看更多内容
DOI：
10.1073/pnas.0605686103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Schneider, D. A.;French, S. L.;Nomura, M.
通讯作者：
Nomura, M.
影响因子：
9.8
作者：
Jouffe C;Cretenet G;Symul L;Martin E;Atger F;Naef F;Gachon F
通讯作者：
Gachon F
影响因子：
16
作者：
Albert, Benjamin;Knight, Britta;Shore, David
通讯作者：
Shore, David
影响因子：
10.5
作者：
通讯作者：
--
影响因子：
11.4
作者：
Wanke, V;Pedruzzi, I;De Virgilio, C
通讯作者：
De Virgilio, C