title: Regulation of SirT1-nucleomethylin binding by rRNA coordinates ribosome biogenesis with nutrient availability.
abstract: Nucleomethylin (NML), a novel nucleolar protein, is important for mediating the assembly of the energy-dependent nucleolar silencing complex (eNoSC), which also contains SirT1 and SUV39H1. eNoSC represses rRNA transcription during nutrient deprivation, thus reducing energy expenditure and improving cell survival. We found that NML is an RNA binding protein that copurifies with 5S, 5.8S, and 28S rRNA. The SirT1 and RNA binding regions on NML showed partial overlap, and the NML-SirT1 interaction was competitively inhibited by rRNA. Nutrient deprivation triggered downregulation of rRNA transcription, reduced the level of NML-associated rRNA, and stimulated NML-SirT1 binding. Assembly of eNoSC facilitated repression of pre-rRNA transcription. These results suggest that nascent rRNA generates a positive-feedback signal by suppressing the assembly of eNoSC and protecting active ribosomal DNA units from heterochromatin formation. This RNA-mediated mechanism enables the eNoSC to amplify the effects of upstream nutrient-responsive regulators.
authors.affiliation: Molecular Oncology Department, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Leixiang
authors.initials: L
authors.lastname: Yang
authors.forename: Tanjing
authors.initials: T
authors.lastname: Song
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.forename: Neha
authors.initials: N
authors.lastname: Kabra
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: John
authors.initials: J
authors.lastname: Koomen
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D012339:RNA, Ribosomal, 28S / Q000235:genetics / Q000378:metabolism; D012340:RNA, Ribosomal, 5.8S / Q000235:genetics / Q000378:metabolism; D012341:RNA, Ribosomal, 5S / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D012339:RNA, Ribosomal, 28S; D012340:RNA, Ribosomal, 5.8S; D012341:RNA, Ribosomal, 5S; D016601:RNA-Binding Proteins; D008780:Methyltransferases; C529371:RRP8 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose
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