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Intricate regulation of ribosome biogenesis genes in response to mTORC1 signaling
bioRxiv - Molecular Biology Pub Date : 2021-01-04 , DOI: 10.1101/2021.01.04.425249
Sanjay Kumar , Muneera Mashkoor , Priya Balamurugan , Anne Grove

Genes encoding ribosomal proteins are repressed in response to inhibition of mTORC1. In Saccharomyces cerevisiae, this involves dissociation of the activator Ifh1p in a process that depends on Utp22p, a protein that also functions in pre-rRNA processing. Ifh1p has a paralog, Crf1p, which can mediate mTORC1 inhibition by acting as a repressor. Ifh1p and Crf1p derive from a common ancestor, which may have acted as both an activator and a repressor. We report here that UTP22 and RRP7, which encodes another pre-rRNA processing factor, are controlled by mTORC1; both gene promoters are bound by Ifh1p, which dissociates on mTORC1 inhibition. Notably, Crf1p acts as an activator as evidenced by reduced expression in a crf1Δ strain. By contrast, Crf1p is required to repress expression of HMO1, which encodes a cofactor involved in communicating mTORC1 activity to target genes. Our data therefore indicate that Crf1p exhibits the dual repressor/activator functions of the Ifh1p-Crf1p ancestor.

中文翻译:

核糖体生物发生基因对mTORC1信号的复杂调控

响应于mTORC1的抑制,抑制了编码核糖体蛋白的基因。在酿酒酵母中,这涉及活化剂Ifh1p的解离,该过程取决于Utp22p,该蛋白在rRNA的前处理中也起作用。Ifh1p具有旁系同源物Crf1p,它可以通过充当阻遏物来介导mTORC1抑制。Ifh1p和Crf1p源自一个共同的祖先,该祖先可能既充当了激活者,又充当了阻遏物。我们在这里报告,UTP22和RRP7编码另一种rRNA前加工因子,由mTORC1控制;两个基因启动子均受Ifh1p结合,后者在mTORC1抑制作用下解离。值得注意的是,Crf1p充当激活剂,crf1Δ菌株中的表达降低证明了这一点。相比之下,需要Crf1p抑制HMO1的表达,它编码参与将mTORC1活性传达给目标基因的辅助因子。因此,我们的数据表明Crf1p具有Ifh1p-Crf1p祖先的双重阻遏物/激活物功能。
更新日期:2021-01-05
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