Related Experiment Video

Updated: Aug 15, 2025

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.3K

mascRNA alleviates STING-TBK1 signaling-mediated immune response through promoting ubiquitination of STING

Yuqing Hu1, Xueyi Li1, Daoyong Wang1

  • 1Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Molecular Immunology
|January 5, 2023
PubMed

Insights

MALAT1-associated small cytoplasmic RNA (mascRNA) suppresses STING signaling by promoting STING protein degradation. This finding suggests mascRNA could treat inflammatory diseases like COVID-19 driven by aberrant STING activity.

Area of Science:

  • Immunology
  • Molecular Biology
  • RNA Biology

Background:

  • MALAT1-associated small cytoplasmic RNA (mascRNA) is a small noncoding RNA with poorly understood functions.
  • Previous research indicated mascRNA modulates Toll-like receptor (TLR) signaling pathways.
  • The role of mascRNA in stimulator of interferon genes (STING) signaling remained unexplored.

Purpose of the Study:

  • To investigate the influence of mascRNA on STING signaling-triggered immune responses.
  • To elucidate the molecular mechanisms by which mascRNA affects STING pathway activation.
  • To assess the therapeutic potential of mascRNA in DNA-induced inflammatory conditions.

Main Methods:

  • Overexpression and depletion of mascRNA in cellular models.
  • Stimulation with cytosolic DNA to activate the STING pathway.
  • Analysis of type I interferon (IFN) and cytokine gene expression.
  • Western blot analysis of STING, phosphorylated TBK1, and STAT1.
  • In vivo studies using a mouse model of DNA-induced lung injury.
  • Assessment of STING ubiquitination and proteasomal degradation.

Main Results:

  • mascRNA overexpression inhibited type I IFN and cytokine production, reduced STING protein levels, and decreased TBK1/STAT1 phosphorylation.
  • mascRNA depletion enhanced type I IFN expression, increased STING abundance, and promoted TBK1/STAT1 phosphorylation.
  • Exogenous mascRNA mitigated lung inflammation and antiviral responses in vivo.
  • mascRNA promotes K48-linked ubiquitination and proteasomal degradation of STING.

Conclusions:

  • mascRNA suppresses STING-TBK1 signaling by enhancing STING proteasomal degradation.
  • This tRNA-like small RNA negatively regulates innate immunity triggered by cytosolic DNA.
  • mascRNA shows promise for treating inflammatory diseases like COVID-19 characterized by aberrant STING signaling and type I IFN pathology.
Keywords:
Innate immunityInterferonMacrophagesSTINGmascRNA

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.5K
Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli07:26

Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli

Published on: December 26, 2020

4.1K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K