GAIT element

Last updated
GAIT element
RF00179.jpg
Identifiers
SymbolGAIT
Rfam RF00179
Other data
RNA type Cis-reg
Domain(s) Eukaryota
SO SO:0000233
PDB structures PDBe

The gamma interferon inhibitor of translation element or GAIT element is a cis-acting RNA element located in the 3'-UTR of the ceruloplasmin (Cp) mRNA.

The GAIT element forms a stem-loop secondary structure. The GAIT element is involved in selective translational silencing of the Cp transcript within monocytic cells, but not hepatic cells. Cp is a multifunctional, copper-containing glycoprotein produced by the liver and secreted into the plasma for its role in copper and iron homeostasis. Ceruloplasmin is also an acute-phase protein produced by monocytes, and its plasma concentration can double during multiple inflammatory conditions through increased Cp production by monocytic cells after stimulation by interferon gamma (IFNγ). Plasma Cp has been reported to be an independent risk factor for cardiovascular disease, including atherosclerosis, carotid restenosis after endarterectomy, and myocardial infarction. Translational silencing of Cp, and possibly other transcripts, mediated by the GAIT element may contribute to the resolution of the local inflammatory response following cytokine activation of macrophages. [1]

The silencing of Cp protein translation in IFN-gamma-stimulated monocytes is accomplished by binding of the IFN-gamma-activated inhibitor of translation (GAIT) inhibitor complex to the GAIT element. [2] The GAIT complex consists of the proteins ribosomal protein L13a, glutamyl-prolyl-tRNA synthetase, NS1-associated protein-1, and glyceraldehyde 3-phosphate dehydrogenase. [3]

Related Research Articles

Interferon Signaling proteins released by host cells in response to the presence of pathogens

Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

Cytokine

Cytokines are a broad and loose category of small proteins important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Their definite distinction from hormones is still part of ongoing research.

Three prime untranslated region

In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally influence gene expression.

Ceruloplasmin

Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.

Interferon gamma

Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with PPD; the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis. In humans, the IFNγ protein is encoded by the IFNG gene.

Innate immune system

The innate immune system is one of the two main immunity strategies found in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.

Interleukin 29

Interleukin-29 (IL-29) is a cytokine and it belongs to type III interferons group, also termed interferons λ (INF-λ). IL-29 plays an important role in the immune response against pathogenes and especially against viruses by mechanisms similar to type I interferons, but targeting primarily cells of epithelial origin and hepatocytes.

CXCL9

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

CXCL10

C-X-C motif chemokine ligand 10 (CXCL10) also known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene. C-X-C motif chemokine 10 is a small cytokine belonging to the CXC chemokine family.

Interferon type II

A sole member makes up the type II interferons (IFNs) that is called IFN-γ (gamma). Mature IFN-γ is an anti-parallel homodimer, which binds to the IFN-γ receptor (IFNGR) complex to elicit a signal within its target cell. IFNGR is made up of two subunits each of molecules designated IFNGR1 and IFNGR2.

Interferon gamma 5 UTR regulatory element

Interferon gamma 5' UTR regulatory elements are a family of regulatory RNAs. This family represents a pseudoknot containing stem-loop structure found in the 5' UTR of interferon-gamma mRNA. This structure is thought to be involved in translational regulation and the pseudoknot has been found to activate protein kinase R (PKR) which is known to be a translational inhibitor. Mutations in the pseudoknot structure have been found to reduce PKR activation and increase the translation of interferon-gamma.

ISG15

Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ISG15 gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response.

PD-L1

Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.

IFNB1

Interferon beta is a protein that in humans is encoded by the IFNB1 gene. The natural and recombinant protein forms have antiviral, antibacterial, and anticancer properties.

EPRS

Bifunctional aminoacyl-tRNA synthetase is an enzyme that in humans is encoded by the EPRS gene.

MNDA

Myeloid cell Nuclear Differentiation Antigen is a protein that in humans is encoded as MNDA gene.

The pluripotency of biological compounds describes the ability of certain substances to produce several distinct biological responses. Pluripotent is also described as something that has no fixed developmental potential, as in being able to differentiate into different cell types in the case of pluripotent stem cells.

miR-132

In molecular biology miR-132 microRNA is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, generally reducing protein levels through the cleavage of mRNAs or the repression of their translation. Several targets for miR-132 have been described, including mediators of neurological development, synaptic transmission, inflammation and angiogenesis.

Interleukin-1 family

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

IFNA16

Interferon alpha-16, also known as IFN-alpha-16, is a protein that in humans is encoded by theIFNA16 gene.

References

  1. Sampath, P; Mazumder B; Seshadri V; Fox PL (2003). "Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region". Mol Cell Biol. 23 (5): 1509–1519. doi:10.1128/MCB.23.5.1509-1519.2003. PMC   151701 . PMID   12588972.
  2. Mazumder B, Sampath P, Fox PL (2005). "Regulation of macrophage ceruloplasmin gene expression: one paradigm of 3'-UTR-mediated translational control". Mol Cells. 20 (2): 167–172. PMID   16267389.
  3. Mazumder B, Sampath P, Fox PL (2006). "Translational control of ceruloplasmin gene expression: beyond the IRE". Biol Res. 39 (1): 59–66. CiteSeerX   10.1.1.476.8189 . doi:10.4067/s0716-97602006000100007. PMID   16629165.