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Updated: May 12, 2026

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Regulation of snoRNAs in cancer: close encounters with interferon
Shreeram C Nallar1, Dhananjaya V Kalvakolanu
1Department of Microbiology & Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine , Baltimore, MD 21201, USA.
Abstract:
The interferon (IFN) family of cytokines regulates many cellular processes, such as transcription, translation, post-translational modifications, and protein degradation. IFNs induce growth inhibition and/or cell death, depending on the cell type, by employing different proteins. This review describes a novel growth-suppressive pathway employed by IFNs that affects rRNA levels. Maturation of rRNA involves numerous noncoding small regulatory RNA-guided processes. These regulatory RNAs, called small nucleolar RNA (snoRNAs), function as a ribonucleoprotein particle (RNP) in the nucleolus. The biogenesis of snoRNPs is dependent on core protein and assembly factors. Our laboratory recently isolated a growth-suppressive protein gene associated with retinoid-IFN-induced mortality (GRIM)-1 using a genetic screen. IFN-inducible GRIM-1 (SHQ1) is an assembly factor that controls one arm of the snoRNP machinery. GRIM-1 inhibits sno/scaRNP formation to induce growth suppression via reduction in mature rRNA levels. Loss of GRIM-1 observed in certain cancers implicates it to be a novel tumor suppressor. Certain snoRNAs have been reported to act as either oncogenes or tumor suppressors in vitro. Recent studies have shown that certain sno/scaRNAs are further processed into micro RNA-like molecules to control translation of protein-coding RNAs. We present a model as to how these small regulatory RNAs influence cell growth and a potential role for GRIM-1 in this process.
Insights
Interferons (IFNs) use the GRIM-1 protein to suppress cell growth by reducing mature ribosomal RNA (rRNA) levels. Loss of GRIM-1 suggests its role as a tumor suppressor in cancer.
Area of Science:
- Cellular Biology
- Molecular Biology
- Cancer Research
Background:
- Interferons (IFNs) are cytokines that regulate crucial cellular processes including growth and survival.
- Ribosome biogenesis, particularly rRNA maturation, is guided by small nucleolar RNAs (snoRNAs) within ribonucleoprotein particles (snoRNPs).
- Dysregulation of cellular processes and small RNAs is implicated in cancer development.
Purpose of the Study:
- To describe a novel interferon-induced pathway that suppresses cell growth by affecting rRNA levels.
- To elucidate the role of the newly identified GRIM-1 (SHQ1) protein in this pathway.
- To explore the potential tumor suppressor function of GRIM-1 and the broader implications of small regulatory RNAs in cell growth and cancer.
Main Methods:
- Genetic screening to identify growth-suppressive genes induced by retinoid-IFN.
- Characterization of the isolated GRIM-1 (SHQ1) protein as an assembly factor for snoRNPs.
- Analysis of GRIM-1's impact on sno/scaRNP formation and mature rRNA levels.
- Review of existing literature on snoRNAs, microRNAs, and their roles in cancer.
Main Results:
- Interferon-inducible GRIM-1 (SHQ1) was identified as a key regulator of snoRNP biogenesis.
- GRIM-1 inhibits sno/scaRNP formation, leading to reduced mature rRNA levels and subsequent growth suppression.
- Loss of GRIM-1 is observed in certain cancers, suggesting its function as a tumor suppressor.
- Small regulatory RNAs, including snoRNAs and their processed microRNA-like molecules, play significant roles in controlling cell growth and translation.
Conclusions:
- GRIM-1 acts as an interferon-inducible factor that suppresses cell growth by modulating rRNA maturation.
- The tumor suppressor role of GRIM-1 in cancer warrants further investigation.
- Small regulatory RNAs represent a critical network influencing cell proliferation and potentially serving as therapeutic targets in oncology.
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