mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability.
mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability.
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mRNA 脱帽激活剂 Pat1 和 Dhh1 调节转录丰度和翻译，以调节细胞对营养可用性的反应。
DOI：
10.1093/nar/gkad584
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发表时间：
2023
影响因子：
14.9
通讯作者：
Hinnebusch,AlanG
中科院分区：
文献类型：
--
作者：
Vijjamarri,AnilKumar;Gupta,Neha;Onu,Chisom;Niu,Xiao;Zhang,Fan;Kumar,Rakesh;Lin,Zhenguo;Greenberg,MiriamL;Hinnebusch,AlanG
我们通过核糖体分析、RNA-Seq、封闭式mRNA笼式分析、RNA聚合酶II芯片-Seq以及缺乏一个或两个因子的突变体的TMT-MS分析，研究了酵母mRNA解夹激活剂Pat1和Dhh1在抑制营养充足的细胞中特定mRNAs的翻译和丰度方面的作用。虽然环境应激反应在Δ和Δ突变体中被激活，但成百上千的非环境应激反应转录本以一种表明在野生型细胞中被Pat1和Dhh1累积抑制的方式被上调。这些mRNAs在突变体中既显示了去帽作用的减少，也显示了转录的减少，这表明在缺乏Dhh1或Pat1的细胞中，mRNA周转受损会驱动转录去抑制。由Dhh1/Pat1刺激的mRNA降解并不是由糟糕的翻译或次优密码子的浓缩所决定的。Pat1和Dhh1还合作减少许多mRNA的翻译和蛋白质生产。显示Pat1/Dhh1协同翻译抑制的转录本包括参与细胞黏附或利用贫氮源尿囊素的mRNAs。Pat1/Dhh1还抑制了许多涉及呼吸作用、非首选碳源或氮源的分解代谢或自噬的转录本；我们获得了突变体呼吸增加和自噬的证据。因此，Pat1和Dhh1是通常仅在营养限制时才被激活的多个途径的转录后抑制物。
We have examined the roles of yeast mRNA decapping-activators Pat1 and Dhh1 in repressing the translation and abundance of specific mRNAs in nutrient-replete cells using ribosome profiling, RNA-Seq, CAGE analysis of capped mRNAs, RNA Polymerase II ChIP-Seq, and TMT-mass spectrometry of mutants lacking one or both factors. Although the Environmental Stress Response (ESR) is activated indhh1Δandpat1Δmutants, hundreds of non-ESR transcripts are elevated in a manner indicating cumulative repression by Pat1 and Dhh1 in wild-type cells. These mRNAs show both reduced decapping and diminished transcription in the mutants, indicating that impaired mRNA turnover drives transcript derepression in cells lacking Dhh1 or Pat1. mRNA degradation stimulated by Dhh1/Pat1 is not dictated by poor translation nor enrichment for suboptimal codons. Pat1 and Dhh1 also collaborate to reduce translation and protein production from many mRNAs. Transcripts showing concerted translational repression by Pat1/Dhh1 include mRNAs involved in cell adhesion or utilization of the poor nitrogen source allantoin. Pat1/Dhh1 also repress numerous transcripts involved in respiration, catabolism of non-preferred carbon or nitrogen sources, or autophagy; and we obtained evidence for elevated respiration and autophagy in the mutants. Thus, Pat1 and Dhh1 function as post-transcriptional repressors of multiple pathways normally activated only during nutrient limitation.
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DOI：
10.1016/s0021-9258(18)33621-4
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
G. Reid;G. Schatz
通讯作者：
G. Schatz
影响因子：
16
作者：
Gatica, Damian;Hu, Guowu;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
影响因子：
10.5
作者：
FORSBURG, SL;GUARENTE, L
通讯作者：
GUARENTE, L
影响因子：
7
作者：
Zhaolian Lu;Zhenguo Lin
通讯作者：
Zhaolian Lu;Zhenguo Lin
影响因子：
16
作者：
Arribere, Joshua A.;Doudna, Jennifer A.;Gilbert, Wendy V.
通讯作者：
Gilbert, Wendy V.