title: GRIM-1, a novel growth suppressor, inhibits rRNA maturation by suppressing small nucleolar RNAs.
abstract: We have recently isolated novel IFN-inducible gene, Gene associated with Retinoid-Interferon-induced Mortality-1 (GRIM-1), using a genetic technique. Moderate ectopic expression of GRIM-1 caused growth inhibition and sensitized cells to retinoic acid (RA)/IFN-induced cell death while high expression caused apoptosis. GRIM-1 depletion, using RNAi, conferred a growth advantage. Three protein isoforms (1α, 1β and 1γ) with identical C-termini are produced from GRIM-1 mRNA. We show that GRIM-1 isoforms interact with NAF1 and DKC1, two essential proteins required for box H/ACA sno/sca RNP biogenesis and suppresses box H/ACA RNA levels in mammalian cells by delocalizing NAF1. Suppression of these small RNAs manifests as inefficient rRNA maturation and growth suppression. Interestingly, yeast Shq1p also caused growth suppression in mammalian cells. Consistent with its growth-suppressive property, GRIM-1 expression is lost in a number of human primary prostate tumors. Our observations support a recent study that GRIM-1 might act as a co-tumor suppressor in the prostate.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland, United States of America.
authors.forename: Shreeram C
authors.initials: SC
authors.lastname: Nallar
authors.forename: Limei
authors.initials: L
authors.lastname: Lin
authors.forename: Varsha
authors.initials: V
authors.lastname: Srivastava
authors.forename: Padmaja
authors.initials: P
authors.lastname: Gade
authors.forename: Edward R
authors.initials: ER
authors.lastname: Hofmann
authors.forename: Hafiz
authors.initials: H
authors.lastname: Ahmed
authors.forename: Sekhar P
authors.initials: SP
authors.lastname: Reddy
authors.forename: Dhananjaya V
authors.initials: DV
authors.lastname: Kalvakolanu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000494:pharmacology; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000235:genetics* / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; C551999:NAF1 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D058727:RNA, Small Untranslated; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C470008:Shq1 protein, S cerevisiae; D014212:Tretinoin; D016899:Interferon-beta