title: mTOR signaling regulates the processing of pre-rRNA in human cells.
abstract: Signaling through the mammalian target of rapamycin, complex 1 (mTORC1), positively regulates the transcription of ribosomal RNA (rRNA) and the synthesis of ribosomal proteins, thereby promoting the complex process of ribosome biogenesis. The major rRNAs are transcribed as a single precursor, which must be processed to create the 5.8S, 18S and 28S rRNAs. We used a new non-radioactive labeling approach to study the effects of rapamycin, an inhibitor of mTORC1, on rRNA synthesis. Rapamycin not only impaired synthesis of new 18S, 28S or 5S rRNA but also induced their decay. This prompted us to examine the effects of rapamycin on rRNA processing. We show that rapamycin also interferes with the processing events that generate 18S and 28S rRNA. rRNA transcription and processing occur in regions of the nucleus known as nucleoli. We find that the mTORC1 components raptor and mTOR are both present in nucleoli, where they may regulate rRNA maturation events. While rapamycin has no effect on overall nucleolar morphology or its proteome, it does induce loss of mTOR and raptor from them. These data show that mTORC1 is located in nucleoli where it acts to regulate events involved in ribosome biogenesis including the maturation of rRNA molecules.
authors: School of Biological Sciences, University of Southampton, SO17 1BJ, UK.
authors: Valentina
authors: V
authors: Iadevaia
authors: Ze
authors: Z
authors: Zhang
authors: Eric
authors: E
authors: Jan
authors: Christopher G
authors: CG
authors: Proud
mesh_terms: D002466:Cell Nucleolus / Q000737:chemistry / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000032:analysis / Q000037:antagonists & inhibitors; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012335:RNA, Ribosomal / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus