Grove Anne
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, 70803, USA.
Curr Genet. 2018 Feb;64(1):131-135. doi: 10.1007/s00294-017-0738-z. Epub 2017 Aug 22.
Under conditions of nutrient limitation and cellular stress, or by addition of rapamycin, the mechanistic target of rapamycin complex 1 (mTORC1) is inhibited. This results in downregulation of genes that encode rRNA and ribosomal proteins. While most of the mTORC1 functions that have been previously characterized at a mechanistic level take place in the cytoplasm, nuclear roles have also been reported, including direct association of TOR kinase with rRNA genes. This review highlights the recent observation that Saccharomyces cerevisiae Tor1p also binds directly to the RNA polymerase II-transcribed gene encoding Hmo1p, a protein that is involved in communicating mTORC1 activity to downstream targets. A reduction in HMO1 mRNA levels in response to DNA damage or addition of rapamycin requires Tor1p, suggesting a role for TOR kinase in control of gene activity by direct binding to target genes. Potential targets for chromatin-bound Tor1p are discussed and the possibility that Tor1p similarly contributes to control of other genes linked to ribosome biogenesis is considered.
在营养限制和细胞应激条件下,或通过添加雷帕霉素,雷帕霉素机制靶点复合物1(mTORC1)会受到抑制。这导致编码rRNA和核糖体蛋白的基因下调。虽然之前在机制层面表征的大多数mTORC1功能发生在细胞质中,但也有核功能的报道,包括TOR激酶与rRNA基因的直接关联。本综述重点介绍了最近的一项观察结果,即酿酒酵母Tor1p也直接与编码Hmo1p的RNA聚合酶II转录基因结合,Hmo1p是一种参与将mTORC1活性传递给下游靶点的蛋白质。响应DNA损伤或添加雷帕霉素时HMO1 mRNA水平的降低需要Tor1p,这表明TOR激酶通过直接结合靶基因在基因活性控制中发挥作用。文中讨论了与染色质结合的Tor1p的潜在靶点,并考虑了Tor1p类似地参与控制与核糖体生物发生相关的其他基因的可能性。