mTOR signaling regulates the processing of pre-rRNA in human cells
Iadevaia, Valentina, Zhang, Ze, Jan, Eric and Proud, Christopher G. (2012) mTOR signaling regulates the processing of pre-rRNA in human cells. Nucleic Acids Research, 40, (6), 2527-2539. (doi:10.1093/nar/gkr1040). (PMID:22121221).
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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.
|Digital Object Identifier (DOI):||doi:10.1093/nar/gkr1040|
|Subjects:||Q Science > QH Natural history > QH426 Genetics
Q Science > QP Physiology
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences > Molecular & Cellular
|Date Deposited:||24 Apr 2012 08:57|
|Last Modified:||06 Aug 2015 03:05|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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