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GRIM-1, a Novel Growth Suppressor, Inhibits rRNA Maturation by Suppressing Small Nucleolar RNAs

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Title: GRIM-1, a Novel Growth Suppressor, Inhibits rRNA Maturation by Suppressing Small Nucleolar RNAs
Author(s): Nallar, Shreeram C.; Lin, Limei; Srivastava, Varsha; Gade, Padmaja; Hofmann, Edward R.; Ahmed, Hafiz; Reddy, Sekhar P.; Kalvakolanu, Dhananjaya V.
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 epletion, using RNAi, conferred a growth advantage. Three protein isoforms (1a, 1b and 1c) 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.
Issue Date: 2011-09
Publisher: Public Library of Science
Citation Info: Nallar, S. C., Lin, L., Srivastava, V., Gade, P., Hofmann, E. R., Ahmed, H., Reddy, S. P., & Kalvakolanu, D. V. 2011. GRIM-1, a Novel Growth Suppressor, Inhibits rRNA Maturation by Suppressing Small Nucleolar RNAs. PLoS One, 6(9). DOI: 10.1371/journal.pone.0024082
Type: Article
Description: Copyright © 2011 Kalvakolanu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.DOI: 10.1371/journal.pone.0024082
ISSN: 1932-6203
Sponsor: NIH grants CA105005 and CA78282 to DVK. SPR is supported by grants HL66109 and ES11863 from the National Institutes of Health. HA is supported by CA133935-01 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Date Available in INDIGO: 2012-03-16

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