SHPRH通过以mTOR依赖的方式识别组蛋白密码来调节核糖体RNA转录。
SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner.
作者信息
Lee Deokjae, An Jungeun, Park Young-Un, Liaw Hungjiun, Woodgate Roger, Park Jun Hong, Myung Kyungjae
机构信息
Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 689-798, Korea.
出版信息
Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):E3424-E3433. doi: 10.1073/pnas.1701978114. Epub 2017 Apr 11.
Abstract
Many DNA repair proteins have additional functions other than their roles in DNA repair. In addition to catalyzing PCNA polyubiquitylation in response to the stalling of DNA replication, SHPRH has the additional function of facilitating rRNA transcription by localizing to the ribosomal DNA (rDNA) promoter in the nucleoli. SHPRH was recruited to the rDNA promoter using its plant homeodomain (PHD), which interacts with histone H3 when the fourth lysine of H3 is not trimethylated. SHPRH enrichment at the rDNA promoter was inhibited by cell starvation, by treatment with actinomycin D or rapamycin, or by depletion of CHD4. SHPRH also physically interacted with the RNA polymerase I complex. Taken together, we provide evidence that SHPRH functions in rRNA transcription through its interaction with histone H3 in a mammalian target of rapamycin (mTOR)-dependent manner.
摘要
许多DNA修复蛋白除了在DNA修复中发挥作用外，还具有其他功能。除了在DNA复制停滞时催化增殖细胞核抗原（PCNA）多聚泛素化外，SHPRH还具有通过定位于核仁中的核糖体DNA（rDNA）启动子来促进rRNA转录的额外功能。SHPRH利用其植物同源结构域（PHD）被招募到rDNA启动子，当组蛋白H3的第四个赖氨酸未被三甲基化时，该结构域与H3相互作用。细胞饥饿、放线菌素D或雷帕霉素处理，或CHD4缺失会抑制rDNA启动子处的SHPRH富集。SHPRH还与RNA聚合酶I复合物发生物理相互作用。综上所述，我们提供了证据表明，SHPRH通过以哺乳动物雷帕霉素靶蛋白（mTOR）依赖的方式与组蛋白H3相互作用，在rRNA转录中发挥作用。
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