Related Experiment Video
Updated: Jun 13, 2025
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
11.9K
SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.
Kristen C Witt1,2,3, Adam Dziulko4, Joohyun An2,3
1Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Nature
|June 11, 2025
Summary
SP140 represses interferon-beta (Ifnb1) mRNA stability by inhibiting RESIST, a regulator of RNA stability. This mechanism reveals SP140
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Type I interferons are crucial for antiviral immunity but require strict regulation.
- SP140, a transcriptional repressor, is known to inhibit interferon-beta (Ifnb1) expression via an uncharacterized mechanism.
Purpose of the Study:
- To elucidate the mechanism by which SP140 regulates Ifnb1 expression.
- To identify novel regulators involved in interferon mRNA stability and antiviral responses.
Main Methods:
- Investigated the direct transcriptional effects of SP140 on Ifnb1.
- Identified and characterized a novel regulator, RESIST, involved in Ifnb1 mRNA stability.
- Assessed the role of SP140 and RESIST in viral replication and interferon regulation.
Main Results:
- SP140 does not directly repress Ifnb1 transcription; instead, it destabilizes Ifnb1 mRNA.
- SP140 achieves this by repressing RESIST, a factor that stabilizes Ifnb1 mRNA against TTP and CCR4-NOT complex activity.
- SP140 exhibits antiviral activity against gammaherpesvirus MHV68, independent of its Ifnb1 regulatory function.
Conclusions:
- SP140 possesses dual functions: regulating interferon production and exhibiting direct antiviral activity.
- SP140 and RESIST are proposed components of antiviral effector-triggered immunity.
More Related Videos
10:00High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
13.3K
12:43Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
12.1K
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
01:23RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K
02:30siRNA - Small Interfering RNAs
16.6K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.6K
02:15Experimental RNAi
6.1K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
01:23Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
02:51mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K