Control of RNA polymerase II-transcribed genes by direct binding of TOR kinase

Abstract

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.

Keywords: DNA damage; HMO1; Rapamycin; Ribosome biogenesis; Yeast; mTORC1.