# G-CSF factor stem-loop destabilising element

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{{Infobox rfam
| Name = G-CSF factor stem-loop destabilising element (SLDE)
| image = RF00183.jpg
| width = 
| caption = Predicted [secondary structure](/source/secondary_structure) and [sequence conservation](/source/sequence_conservation) of G-CSF_SLDE
| Symbol = G-CSF_SLDE
| AltSymbols = 
| Rfam = RF00183
| miRBase = 
| miRBase_family = 
| RNA_type = [Cis-reg](/source/Cis-regulatory_element)
| Tax_domain = [Eukaryota](/source/Eukaryota)
| GO = 
| SO = {{SO|0000233}} 
| CAS_number = 
| EntrezGene = 
| HGNCid = 
| OMIM = 
| PDB = 
| RefSeq = 
| Chromosome = 
| Arm = 
| Band = 
| LocusSupplementaryData = 
}}

The '''G-CSF factor stem-loop destabilising element (SLDE)''' is an [RNA element](/source/cis-regulatory_element) secreted by [fibroblast](/source/fibroblast)s and [endothelial cells](/source/endothelial_cells) in response to the inflammatory mediators [interleukin-1](/source/interleukin-1) (IL-1) and [tumour necrosis factor-alpha](/source/tumour_necrosis_factor-alpha) and by activated [macrophage](/source/macrophage)s. The synthesis of G-CSF is regulated both [transcriptionally](/source/transcription_(genetics)) and through control of [mRNA](/source/mRNA) stability. In unstimulated cells G-CSF mRNA is unstable but becomes stabilised in response to IL-1 or tumour necrosis factor alpha, and also in the case of [monocyte](/source/monocyte)s and macrophages, in response to [lipopolysaccharide](/source/lipopolysaccharide). It is likely that the presence of the SLDE in the G-CSF mRNA contributes to the specificity of regulation of G-CSF mRNA and enhances the rate of shortening of the [poly(A) tail](/source/polyadenylation).<ref>{{cite journal | vauthors = Putland RA, Sassinis TA, Harvey JS, Diamond P, Coles LS, Brown CY, Goodall GJ | title = RNA destabilization by the granulocyte colony-stimulating factor stem-loop destabilizing element involves a single stem-loop that promotes deadenylation | journal = Molecular and Cellular Biology | volume = 22 | issue = 6 | pages = 1664–1673 | date = March 2002 | pmid = 11865046 | pmc = 135610 | doi = 10.1128/MCB.22.6.1664-1673.2002 }}</ref>

[Adenylate uridylate-rich elements](/source/AU-rich_element) (AUREs) are present in other cytokine mRNAs, but the SLDE is the most important element that stabilizes G-CSF mRNA in response to IL-1 or tumor necrosis factor- alpha.<ref>{{cite journal | vauthors = Brown CY, Lagnado CA, Goodall GJ | title = A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 24 | pages = 13721–13725 | date = November 1996 | pmid = 8943001 | pmc = 19403 | doi = 10.1073/pnas.93.24.13721 | bibcode = 1996PNAS...9313721B | doi-access = free }}</ref> Additionally, there are destabilizing elements similar to SLDE found in [IL-2](/source/Interleukin_2) and [IL-6](/source/Interleukin_6). The 3'-UTR of G-CSF mRNA contains a destabilizing element that is insensitive to [calcium ionophore](/source/Calcium_Ionophore_A23187), hence SLDE regulates G-CSF mRNA. AUDEs do not function in 5637 Bladder carcinoma cells, but the SLDE does. The two destablizing elements, SLDE and AURE, provide multiple mechanisms to regulate cytokine expression.

[Neutrophil](/source/Neutrophil)s, are the most abundant type of [granulocyte](/source/granulocyte)s and are responsible for leading the first response of the immune system response against invaders. Granulocyte-colony stimulating factor (G-CSF) is a [glycoprotein](/source/glycoprotein) that stimulates proliferation of neutrophil [progenitor cell](/source/progenitor_cell)s and leads to the maturation of neutrophils. [monocyte](/source/monocyte)s and [macrophage](/source/macrophage)s are the cells that secrete G-CSF, but it is found that [endothelial cells](/source/Endothelium), [fibroblasts](/source/Fibroblast), and [bone marrow stromal cells](/source/Bone_marrow) also secrete the glycoprotein. Expression of G-CSF glycoprotein is complex and has both transcription and post transcription regulation. Two specific types of [regulatory elements](/source/Regulatory_sequence) are present in the [3' untranslated region](/source/Three_prime_untranslated_region) (3'UTR) of G-CSF [mRNA](/source/Messenger_RNA). These elements are referred to as adenylate uridylate-rich elements (AUREs) and stem-loop destabilizing element (SLDE). They have been shown to be destabilizing elements of the G-CSF mRNA. On the other hand, the stability of the mRNA is regulated by [p38 mitogen-activated protein kinase](/source/P38_mitogen-activated_protein_kinases) (MAPK) and this phosphorylating enzyme has been shown to be linked to the AUREs in the 3'UTR.

SB203580 specifically inhibits the [catalytic activity](/source/Catalysis) of p38 MAPK by competitively binding to the active site where [ATP](/source/ATP_synthase) is supposed to bind and is used to probe the role of p38 MAPK in cells.<ref>{{cite journal | vauthors = Chang SF, Li HC, Huang YP, Tasi WJ, Chou YY, Lu SC | title = SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3' untranslated region in macrophages independently of its effect on p38 MAPK activity | journal = Journal of Biomedical Science | volume = 23 | issue = 1 | pages = 3 | date = January 2016 | pmid = 26772539 | pmc = 4715298 | doi = 10.1186/s12929-016-0221-z | doi-access = free }}</ref> SB203580 amplified the lipopolysaccharide-induced increase in the G-CSF mRNA levels in mouse [bone marrow-derived macrophages](/source/Bone_marrow-derived_macrophage) and in THP-1 human macrophages. By displaying that the decay of G-CSF mRNA, in the presence of [actinomycin D](/source/Dactinomycin), was slower in SB203580-treated cells. SB203580 increased the stability of G-CSF mRNA. SLDE is essential for the SB203580-induced increase in the stability of mRNA.{{short description|RNA element}}

== References ==
{{reflist}}

== External links ==
* {{Rfam|id=RF00183|name=G-CSF factor stem-loop destabilising element (SLDE)}}

Category:Cis-regulatory RNA elements
{{molecular-cell-biology-stub}}

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Adapted from the Wikipedia article [G-CSF factor stem-loop destabilising element](https://en.wikipedia.org/wiki/G-CSF_factor_stem-loop_destabilising_element) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/G-CSF_factor_stem-loop_destabilising_element?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.