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Selective inhibition of 28S ribosomal RNA in macrophages activated by interferon-gamma or -beta
Abstract:
We have investigated the metabolism of RNA in mouse peritoneal exudate macrophages activated by interferon (IFN)-gamma or -beta. Both species of IFN induce cytotoxic activity in macrophages. We observed a decrease in the incorporation of [3H]-uridine into total RNA in macrophages treated with doses of IFN that induce cytotoxic activity. IFN-gamma was 100-fold to 1000-fold more potent that IFN-beta in inhibiting RNA synthesis. [3H]Uridine-labeled RNA was purified from IFN-activated and control macrophages and was size fractionated on agarose gels. Macrophages activated by either IFN-gamma or IFN-beta had an imbalanced accumulation of 28S ribosomal RNA compared with their accumulation of 18S ribosomal RNA. Pulse-chase experiments suggested that IFN induced a selective inhibition of the processing of 28S ribosomal RNA. These results provide the first evidence that IFN can modulate ribosomal gene expression at the post-transcriptional level. Moreover, they indicate that inhibition of 28S ribosomal RNA accumulation in macrophages is a molecular event triggered by IFN-gamma, as well as IFN-beta.
Insights
Interferons (IFN) activate macrophages, decreasing RNA synthesis and selectively inhibiting 28S ribosomal RNA processing. This reveals interferons modulate ribosomal gene expression post-transcriptionally in macrophages.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Interferons (IFN) are crucial cytokines involved in immune responses.
- IFN-gamma and IFN-beta activate macrophages, inducing cytotoxic activity.
- Understanding the molecular mechanisms of IFN action is vital.
Purpose of the Study:
- To investigate the effects of IFN-gamma and IFN-beta on RNA metabolism in mouse macrophages.
- To determine if IFNs modulate ribosomal RNA synthesis or processing.
- To elucidate the post-transcriptional regulation of ribosomal gene expression by IFNs.
Main Methods:
- Macrophages were activated with IFN-gamma or IFN-beta.
- Incorporation of [3H]-uridine into total RNA was measured.
- RNA was purified, size-fractionated using agarose gel electrophoresis.
- Pulse-chase experiments were performed to assess RNA processing.
Main Results:
- IFN treatment decreased [3H]-uridine incorporation into total RNA.
- IFN-gamma was significantly more potent than IFN-beta in inhibiting RNA synthesis.
- A selective inhibition of 28S ribosomal RNA processing was observed in IFN-activated macrophages.
- Imbalanced accumulation of 28S vs. 18S ribosomal RNA occurred.
Conclusions:
- IFNs modulate ribosomal gene expression at the post-transcriptional level.
- Selective inhibition of 28S ribosomal RNA accumulation is a molecular event triggered by both IFN-gamma and IFN-beta.
- These findings provide novel insights into the molecular mechanisms of interferon-mediated immune responses.